Liam Welsh

Spirometry centile charts for young Caucasian children: The asthma UK collaborative initiative

RATIONALE Advances in spirometry measurement techniques have made it possible to obtain measurements in children as young as 3 years of age; however, in practice, application remains limited by the lack of appropriate reference data for young children, which are often based on limited population-specific samples. OBJECTIVES We aimed to build on previous models by collating existing reference data in young children (aged 3-7 yr), to produce updated prediction equations that span the preschool years and that are also linked to established reference equations for older children and adults. METHODS The Asthma UK Collaborative Initiative was established to collate lung function data from healthy young children aged 3 to 7 years. Collaborators included researchers with access to pulmonary function test data in healthy preschool children. Spirometry centiles were created using the LMS (lambda, micro, sigma) method and extend previously published equations down to 3 years of age. MEASUREMENTS AND MAIN RESULTS The Asthma UK centile charts for spirometry are based on the largest sample of healthy young Caucasian children aged 3-7 years (n = 3,777) from 15 centers across 11 countries and provide a continuous reference with a smooth transition into adolescence and adulthood. These equations improve existing pediatric equations by considering the between-subject variability to define a more appropriate age-dependent lower limit of normal. The collated data set reflects a variety of equipment, measurement protocols, and population characteristics and may be generalizable across different populations. CONCLUSIONS We present prediction equations for spirometry for preschool children and provide a foundation that will facilitate continued updating.

Nature and severity of lung function abnormalities in extremely pre-term children at 11 years of age

Advances in neonatal care have resulted in increased survival of children born extremely pre-term (EP). Nevertheless the incidence of bronchopulmonary dysplasia and long-term respiratory morbidity remains high. We investigated the nature of pathophysiological changes at 11 yrs of age to ascertain whether respiratory morbidity in EP children primarily reflects alterations in the lung periphery or more centralised airway function in this population. Spirometry, plethysmography, diffusing capacity, exhaled nitric oxide, multiple-breath washout, skin tests and methacholine challenge were used during laboratory-based assessments in a subgroup of the 1995 EPICure cohort and in controls. Results were obtained in 49 EP and 52 control children. Lung function abnormalities were found in 78% of EP children, with evidence of airway obstruction, ventilation inhomogeneity, gas trapping and airway hyperresponsiveness. Levels of atopy and exhaled nitric oxide were similar between the groups. Prior wheeze was associated with significant reductions in forced flows and volumes. By contrast, abnormalities of the lung periphery appear to be mediated primarily through EP birth per se. The prevalence of lung function abnormalities, which is largely obstructive in nature and likely to have long-term implications, remains high among 11-yr-old children born EP. Spirometry proved an effective means of detecting these persistent abnormalities.

Longitudinal study of childhood wheezy bronchitis and asthma: outcome at age 42

Longitudinal studies have reported that asthma in childhood has a good prognosis. However, most of these studies have not taken into account the severity of childhood symptoms.1 The Melbourne Epidemiological Study of Childhood Asthma recruited children at age 7 years and followed them up through adolescence to adulthood.2–5 This report describes outcome at age 42 years in relation to symptoms in childhood. In 1964, 401 children (295 with asthma and 106 controls) were randomly selected from a total of 30 000 7 year olds living in metropolitan Melbourne. A further 83 children with severe asthma were included from the same cohort in 1967, at age 10. 2 3 Original data were available for 479 participants. …

Reference equations for specific airway resistance in children: the Asthma UK initiative

Plethysmographic specific airway resistance (sRaw) is a useful research method for discriminating lung disease in young children. Its use in clinical management has, however, been limited by lack of consensus regarding equipment, methodology and reference data. The aim of our study was to collate reference data from healthy children (3–10 yrs), document methodological differences, explore the impact of these differences and construct reference equations from the collated dataset. Centres were approached to contribute sRaw data as part of the Asthma UK initiative. A random selection of pressure–flow plots were assessed for quality and site visits elucidated data collection and analysis protocols. Five centres contributed 2,872 measurements. Marked variation in methodology and analysis excluded two centres. sRaw over-read sheets were developed for quality control. Reference equations and recommendations for recording and reporting both specific effective and total airway resistance (sReff and sRtot, respectively) were developed for White European children from 1,908 measurements made under similar conditions. Reference sRaw data collected from a single centre may be misleading, as methodological differences exist between centres. These preliminary reference equations can only be applied under similar measurement conditions. Given the potential clinical usefulness of sRaw, particularly with respect to sReff, methodological guidelines need to be established and used in prospective data collection.

Childhood Wheeze Phenotypes Show Less Than Expected Growth in FEV1 across Adolescence

RATIONALE Better characterization of childhood wheeze phenotypes using newer statistical methods provides a basis for addressing the heterogeneity of childhood asthma. Outcomes of these phenotypes beyond childhood are unknown. OBJECTIVES To determine if adolescent respiratory symptoms, lung function, and changes in lung function over adolescence differ by childhood wheeze phenotypes defined through latent class analysis. METHODS A prospective birth cohort (Melbourne Atopy Cohort Study) followed 620 high allergy-risk children, recording respiratory symptoms and spirometry at 12 and 18 years. Regression analyses identified relationships between wheeze phenotypes (never/infrequent, early transient, early persistent, intermediate onset, and late onset) and lung function, change in lung function (12-18 yr), respiratory symptoms, and asthma. The baseline classification was never/infrequent wheeze. MEASUREMENTS AND MAIN RESULTS Deficits in expected growth of lung function, measured by change in prebronchodilator FEV1 between 12 and 18 years, were found for early persistent (reduced 290 ml; 95% confidence interval [CI], 82-498), intermediate-onset (reduced 210 ml; 95% CI, 62-359), and late-onset wheeze (reduced 255 ml; 95% CI, 69-442). Intermediate-onset wheezers had persistent FEV1 deficit after bronchodilator at 18 years (reduced 198 ml; 46,350). Current asthma risk was increased for all phenotypes except early transient, which was also not associated with lung function deficits at 12 or 18 years. CONCLUSIONS Persistent wheeze phenotypes in childhood were associated with reduced growth in prebronchodilator FEV1 over adolescence. Intermediate-onset wheezers showed irreversible airflow limitation by 18 years. Conversely, early transient wheeze was a benign condition with no sequelae for respiratory health by age 18.

Lung clearance index in cystic fibrosis subjects treated for pulmonary exacerbations

Pulmonary exacerbations are important clinical events for cystic fibrosis (CF) patients. Studies assessing the ability of the lung clearance index (LCI) to detect treatment response for pulmonary exacerbations have yielded heterogeneous results. Here, we conduct a retrospective analysis of pooled LCI data to assess treatment with intravenous antibiotics for pulmonary exacerbations and to understand factors explaining the heterogeneous response. A systematic literature search was performed to identify prospective observational studies. Factors predicting the relative change in LCI and spirometry were evaluated while adjusting for within-study clustering. Six previously reported studies and one unpublished study, which included 176 pulmonary exacerbations in both paediatric and adult patients, were included. Overall, LCI significantly decreased by 0.40 units (95% CI −0.60– −0.19, p=0.004) or 2.5% following treatment. The relative change in LCI was significantly correlated with the relative change in forced expiratory volume in 1 s (FEV1), but results were discordant in 42.5% of subjects (80 out of 188). Higher (worse) baseline LCI was associated with a greater improvement in LCI (slope: −0.9%, 95% CI −1.0– −0.4%). LCI response to therapy for pulmonary exacerbations is heterogeneous in CF patients; the overall effect size is small and results are often discordant with FEV1. Lung clearance index response to therapy for pulmonary exacerbations is heterogeneous in cystic fibrosis patients http://ow.ly/Mnvtd

Increased rate of lung function decline in Australian adolescents with cystic fibrosis

Though baseline lung function as measured by spirometry in children with cystic fibrosis (CF) has improved, the annual rate of decline has not changed significantly during the critical period of adolescence. The aim of this study was to describe factors associated with longitudinal decline in lung function in a contemporary cohort of children with CF.

Benefits of whole-body vibration to people with COPD: a community-based efficacy trial

BackgroundBenefits of community-based whole-body vibration (WBV) as a mode of exercise training for people with chronic obstructive pulmonary disease (COPD) have not been investigated. The low skill demand of WBV may enhance habitual sustainability to physical activity by people with COPD, provided efficacy of WBV can be established. The purpose of this trial was to compare a community-based WBV intervention with a sham WBV (SWBV) intervention and monitor exacerbations, exercise tolerance, and functional performance of the lower limbs of people with COPD.MethodsCommunity-dwelling adults with a GOLD clinical diagnosis of COPD were recruited to the trial. This was a Phase II efficacy trial with crossover to sham intervention interspersed with two-week washout. Each six-week intervention consisted of two sessions per week of either WBV or SWBV. The interventions were completed in the home of each participant under supervision. The outcome measures were selected psychological (perceived dyspnoea) and physiological (heart rate and oxygen saturation) responses to exercise, simulated activities of daily living (timed-up-and got test and 5-chair stands test), and selected kinematic variables of gait across the 14-week trial.ResultsSixteen adults with stable COPD were recruited to the trial. No exacerbations were reported during the WBV or SWBV interventions. After WBV, performance of activities of daily living (ADLs) and gait improved (p ≤ 0.05), while there was no change after SWBV (p > 0.05). Despite five withdrawals during the washout period, a 100% compliance to each six-week intervention was noted.ConclusionsResults showed that WBV did not exacerbate symptoms of COPD that can be associated with physical inactivity. The WBV intervention improved tests to simulate ADLs such as rising from a chair, turning, and walking gait with greater effect than a SWBV intervention. If a placebo effect was systemic to the WBV intervention, the effect was negligible. As a standalone community-based intervention, WBV was an efficacious mode of exercise training for people with stable COPD that did not negatively effect exercise tolerance or exacerbate the disease, while concurrently improving functional performance of the lower limbs.Trial registrationAustralian and New Zealand Clinical Trials Registry ACTRN12612000508875.

Lung clearance index during hospital admission in school-age children with cystic fibrosis

BACKGROUND There is currently limited information regarding lung clearance index (LCI) and its response to treatment of pulmonary exacerbations in CF. We aimed to examine the utility of LCI for assessing short term clinical response to IV antibiotic therapy in school-age children with CF. METHODS Subjects experiencing exacerbations and hospitalised for IV antibiotics performed both multiple breath nitrogen washout (MBNW) and spirometry on admission to hospital and prior to discharge. RESULTS 27 patients (aged 6-20 years) had paired data for MBNW and spirometry. Mean LCI reduced from 12.18 to 11.65 (4.4%) by time of discharge and FEV1z-score improved from -3.05 to -2.86 (6.2%). Overall, LCI improved in n=15 (55%) patients compared with n=18 (67%) where FEV1 improved. CONCLUSIONS In summary, these findings do not support the use of LCI (or indeed, FEV1) to gauge the short term clinical response to IV antibiotic therapy in school-age children with cystic fibrosis.

Efficacy of a whole-body vibration intervention to effect exercise tolerance and functional performance of the lower limbs of people with chronic obstructive pulmonary disease

BackgroundChronic obstructive pulmonary disease (COPD) is a respiratory condition characterised by dyspnoea, excessive sputum production, chronic cough, bronchitis and emphysema. Functionally, exercise tolerance is poor for people with COPD and is linked to difficulty in performing daily tasks. More specifically, exercise difficulties are due partly to dyspnoea and lower limb skeletal muscle dysfunction. The benefit of exercise that does not exacerbate the disease while improving exercise tolerance is salient. Whole-body vibration (WBV) is a mode of physical activity known to improve muscular function of the lower limbs, yet efficacy has not been investigated for a WBV intervention conducted in a home-based setting for people with COPD.Methods/designThis clinically registered trial is a non-randomised placebo cross-over intervention based in the home of each participant (ACTRN12612000508875). Participants diagnosed with COPD will complete a six-week WBV intervention and then after a two-week washout period, will complete a six-week placebo training intervention. Participants will complete sessions twice a week. The duration of the trial is 14 weeks. Community-dwelling older adults with COPD will provide informed voluntary consent to participate. Outcome measures will include immediate, acute, and long-term responses to exercise.DiscussionQuantifying responses to WBV among people with COPD will allow discussion of efficacy of WBV as a mode of physical activity. The skill required by the participant to perform physical activity with WBV is not demanding and may enhance habitual sustainability. The results of this trial could be used to support further research in both clinical and community settings.Trial registrationAustralian New Zealand Clinical Trials Registry (ANZCTR12612000508875)