Gary Connett

British guideline on the management of asthma: A national clinical guideline

These guidelines have been replaced by British Guideline on the Management of Asthma. A national clinical guideline. Superseded By 2012 Revision Of 2008 Guideline: British Guideline on the Management of Asthma. Thorax 2008 May; 63(Suppl 4): 1–121.

Prevention of viral induced asthma attacks using inhaled budesonide.

Thirty two preschool children were entered into a double blind, placebo controlled study using intermittent budesonide to treat viral induced wheeze. Active treatment was either 800 micrograms twice a day via a spacer or 1600 micrograms twice a day via a spacer and facemask in those children too young to use a mouthpiece. Treatment was started at the onset of an upper respiratory tract infection and continued for seven days or until symptoms had resolved for 24 hours. Each child remained in the study until they had completed using one pair of budesonide and placebo inhalers in random order without the need for additional oral prednisolone. Twenty five children completed 28 treatment pairs. All 25 families were asked to express a preference after completing their first treatment pair: 12 preferred budesonide and six preferred placebo; seven had no preference. Symptom scores were compared in 17 treatment pairs that were completed without the need for oral prednisolone. Mean day and night time wheeze in the first week after infection were significantly lower in those receiving budesonide. Intermittent inhalation of budesonide can modify the severity of wheezing in preschool children developing asthma after viral respiratory infections but improvements were modest with the doses used in this study.

Use of 16S rRNA Gene Profiling by Terminal Restriction Fragment Length Polymorphism Analysis To Compare Bacterial Communities in Sputum and Mouthwash Samples from Patients with Cystic Fibrosis

ABSTRACT The bacterial communities present in the oral cavity and the lungs of 19 adult cystic fibrosis (CF) patients were compared by using terminal restriction fragment length polymorphism analysis of 16S rRNA gene PCR products amplified from nucleic acids extracted directly from bacteria in clinical samples. Sputum samples were not found to be subject to profound contamination by oral cavity bacteria. Evidence of colonization of the CF lung by certain oral bacterial species was found.

Cystic Fibrosis Diagnosed After 2 Months of Age Leads to Worse Outcomes and Requires More Therapy

OBJECTIVE. Newborn screening for cystic fibrosis remains controversial because improved pulmonary function has not been established. Studies to date have not accounted for differences in treatments delivered to clinically diagnosed children and newborn-screened controls. Here, we compare outcomes and treatment of patients clinically diagnosed within the newborn-screening reporting window (early-clinically diagnosed), those presenting after this period (late-clinically diagnosed), and patients diagnosed by newborn screening. PATIENTS AND METHODS. In a cross-sectional analysis of cohorts retrospectively ascertained, patients who were homozygous ΔF508 with cystic fibrosis, attending specialist cystic fibrosis centers, and 1 to 10 years of age between 2000 and 2002 were identified from the United Kingdom Cystic Fibrosis Database and stratified into newborn-screened, early-clinically diagnosed, or late-clinically diagnosed cohorts. Two analyses were performed: (1) after restricting to the most recent year of data collection, early-clinically diagnosed and late-clinically diagnosed cohorts were matched to newborn-screened patients by patient age and year of data collection (133 patients per cohort were identified); and (2) for all years of data collection, annual sets of data for early-clinically diagnosed and late-clinically diagnosed patients were matched to newborn-screened patients by patient age and year of data collection (291 data sets per cohort were identified). Median height and weight z scores, proportion of patients with height and weight <10th percentile, prevalence of chronic Pseudomonas aeruginosa infection, Shwachman-Kulczyki morbidity scores, percent predicted forced expiratory volume in 1 second, and numbers of long-term therapies were compared. RESULTS. In both analyses, newborn screening was associated with higher height z score, higher Shwachman-Kulczyki score, lower likelihood of height <10th percentile, and fewer long-term therapies compared with late-clinically diagnosed patients. No other differences were found. CONCLUSIONS. Newborn screening was associated with improved growth, reduced morbidity, and reduced therapy, yet generated equivalent pulmonary outcome compared with late clinical diagnosis, suggesting that newborn screening may slow cystic fibrosis lung disease progression.

A randomised controlled trial to assess the relative benefits of large volume spacers and nebulisers to treat acute asthma in hospital

OBJECTIVES To compare the clinical effectiveness, acceptability, and cost benefit of administering β2 agonists by means of a metered dose inhaler and large volume spacer with conventional nebulisers to children admitted to hospital with acute asthma. METHODS A randomised controlled trial was conducted over five months. Sixty one children older than 3 years admitted to a large teaching hospital and a district general hospital with acute asthma completed the study. Children received either 5 mg of salbutamol up to one hourly by jet nebuliser, or up to 10 puffs of salbutamol 100 μg by means of a metered dose inhaler and spacer up to one hourly. RESULTS Median hospital stay was 40 hours in the nebuliser group and 36.5 hours in the spacer group. Asthma disability scores at two weeks after discharge were significantly improved in the spacer group. Drug costs were £14.62 less for each patient in the spacer group. CONCLUSIONS Large volume spacers are an acceptable, cost effective alternative to nebulisers in treating children admitted with acute asthma, provided that the children can use the mouthpiece, and symptoms are not severe. Their use facilitates effective home treatment by parents, with subsequent reduction in morbidity and re-admission rates.

Prednisolone and salbutamol in the hospital treatment of acute asthma.

The use of oral prednisolone (2 mg/kg) to treat children admitted to hospital with acute asthma was assessed in a placebo controlled study. Children were further randomised to receive either 0.15 mg/kg salbutamol every 30 minutes for the first three hours of admission, or 5 mg salbutamol every one to four hours as needed. Treatment was double blind and the assessor was unaware of the nebuliser regimen given. Children were examined before and after treatment with salbutamol on arrival and reassessed four hours after admission. Seventy children completed the study. Seventeen (46%) of 37 children receiving prednisolone and six (9%) of 33 receiving placebo were fit for discharge after four hours of treatment. There was no significant difference between the two nebuliser regimens. Clinical parameters indicative of asthma severity were improved in all groups. Between group comparisons at reassessment showed higher peak flows in those receiving prednisolone and nebulisers every 30 minutes but differences were not significant for other parameters. Objective parameters indicating steroid efficacy over placebo were minimal. Despite this, those receiving prednisolone were more readily identifiable as being fit for discharge within four hours of treatment.

Impact of antibiotic treatment for pulmonary exacerbations on bacterial diversity in cystic fibrosis

BACKGROUND A diverse array of bacterial species is present in the CF airways, in addition to those recognised as clinically important. Here, we investigated the relative impact of antibiotics, used predominantly to target Pseudomonas aeruginosa during acute exacerbations, on other non-pseudomonal species. METHODS The relative abundance of viable P. aeruginosa and non-pseudomonal species was determined in sputa from 12 adult CF subjects 21, 14, and 7 days prior to antibiotics, day 3 of treatment, the final day of treatment, and 10-14 days afterwards, by T-RFLP profiling. RESULTS Overall, relative P. aeruginosa abundance increased during antibiotic therapy compared to other bacterial species; mean abundance pre-antibiotic 51.0±36.0% increasing to 71.3±30.4% during antibiotic (ANOVA: F(1,54)=5.16; P<0.027). Further, the number of non-pseudomonal species detected fell; pre-antibiotic 6.0±3.3 decreasing to 3.7±3.3 during treatment (ANOVA: F(1,66)=5.11; P<0.027). CONCLUSIONS Antibiotic treatment directed at P. aeruginosa has an additional significant impact on non-pseudomonal, co-colonising species.

Use of a reformulated Oka strain varicella vaccine (SmithKline Beecham Biologicals/Oka) in healthy children

The first live-attenuated Oka strain varicella vaccines needed to be stored at −20°C. Reformulation of this vaccine by SmithKline Beecham Biologicals has provided a vaccine shelf life of up to 2 years when stored at +2°C to +8°C. In this study the immunogenicity and reactogenicity of two different production lots of this reformulated vaccine at two different titres each, which corresponded to the release and expected expiry titres, were evaluated. A double-blind randomised clinical trial was conducted in healthy children aged from 9 to 24 months. Immunogenicity was assessed by the measurement of varicella specific antibodies in paired serum samples taken before and from 35 to 63 days post vaccination. Reactogenicity was assessed by the evaluation of any untoward reactions occurring up to 42 days post vaccination. In order to assess protective efficacy, parents of these subjects were contacted approximately 6 months after completion of the trial. One hundred and ninety-one subjects were recruited into the study. Of the 181 initially seronegative subjects who completed the trial according to the protocol, 179 showed seroconversion (98.9%). Reactions to the vaccine were minor and observed in 46/191 (24%) of subjects. Rashes were present in 19, fever in 22, and both fever and rashes in 5. Rashes were mainly maculo-papular in nature but were vesicular in 6. Febrile reactions were shortlived. After a 6-month follow up period, attenuated varicella with minor clinical symptoms was diagnosed in 6/52 vacinees who had close contact with natural varicella (attack rate=11.5%).

Lung function reference values in Singaporean children aged 6-18 years.

BACKGROUND--A study was undertaken to produce reference values of lung function in Chinese children and a means of calculating adjusted standard deviation scores of lung function for Malay and Indian ethnic groups. METHODS--A cross sectional study of lung function (forced expiratory volume in one second and forced vital capacity) measured with a Jaeger spirometer was performed in a representative sample of Singaporean children made up of 1403 Chinese, 335 Malays, and 206 Indians. RESULTS--The relation between natural logarithms of lung function and height was approximately linear until 150 cm in boys and 140 cm in girls. At these heights there were abrupt changes in the gradients of both lines. Separate regression lines were derived for heights above and below these inflection points. Significant differences in lung function were seen in Chinese compared with Malay and Indian children. In particular, values were considerably lower among Indian boys. CONCLUSIONS--The relation between lung function and height in Chinese children is best described by two regression equations over separate height ranges. Information is provided for the calculation of reference values and standard deviation scores, together with the correction factors that need to be applied to derive these values in Malay and Indian children.

A Population-Based Study of Fish Allergy in the Philippines, Singapore and Thailand

Background: Fish allergy is the third most common food allergy after milk and egg in parts of Europe, but there is little data about prevalence in South East Asia where it is an important part of regular diets. Objective: We aimed to obtain an estimate of the population prevalence of fish allergy among older children in the Philippines, Singapore and Thailand. Methods: The population prevalence of fish allergy in 14- to 16-year-old children in the 3 countries was evaluated using a structured written questionnaire which was distributed to students of randomly selected secondary schools. An extended questionnaire to determine convincing fish allergy on the basis of typical clinical manifestations within 2 h of ingestion was administered to those with positive responses. Results: From acohort of 25,842 students, responses were 81.1% in the Philippines (n = 11,434), 67.9% in Singapore (n = 6,498) and 80.2% (n = 2,034) in Thailand. Using criteria for convincing food allergy, fish allergy was much higher in the Philippines [2.29%, 95% confidence interval (CI) 2.02–2.56] than in Singapore (0.26%, 95% CI 0.14–0.79) and Thailand (0.29%, 95% CI 0.06–0.52). Weighted multiple logistic regression analyses showed that compared to the Philippines, prevalence rates were lower in Singapore [odds ratio (OR) 0.40, 95% CI 0.27–0.60, p < 0.0001] and Thailand (OR 0.13, 95% CI 0.05–0.33, p < 0.0001). Females were more likely to have fish allergy compared to males for all children combined (OR 1.32, 95% CI 1.11–1.58, p = 0.002). Most allergies appeared mild, as only 28% of cases sought medical consultation at the time of the reaction and 31.2% of cases reported continued exposure despite allergic symptoms. Conclusion: Fish allergy in late childhood is more common in the Philippines compared to Singapore and Thailand. Differences in food processing, dietary habits and other cultural practices might be important risk factors for the development of fish allergy in these populations.