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.

Longitudinal evaluation of airway function 21 years after preterm birth.

RATIONALE: There are limited longitudinal data about respiratory morbidity and lung function after preterm birth into adulthood. OBJECTIVES: To determine the evolution of respiratory symptoms, spirometry, and airway hyperresponsiveness of ex-preterm subjects from childhood into adulthood. METHODS: Ex-preterm subjects (median birth weight, 1,440 g; median gestation, 31.5 wk), recruited at birth (not treated with surfactant), had excess respiratory symptoms, airway obstruction, and increased airway hyperresponsiveness in mid-childhood. At a median age of 21.7 years, 60 of these subjects (the index study group) and 50 healthy term control subjects were recruited to determine respiratory morbidity and spirometry. MEASUREMENTS AND MAIN RESULTS: Respiratory symptom questionnaire, spirometry, and methacholine challenge test. The index study group had significantly more respiratory symptoms (16 of 60) than did control subjects (4 of 50) (odds ratio, 4.2; 95% confidence interval, 1.3 to 13.5; P = 0.01), but no significant difference in measured spirometry. Specifically, in the index study group and control subjects, the mean z scores (95% confidence interval of the group difference) for the FEV(1) were -0.60 and -0.58 (-0.44 to 0.49), respectively (P = 0.92); for the forced mid-expiratory flow they were -1.02 and -0.86 (-0.33 to 0.64), respectively (P = 0.52); and for the FVC they were -0.29 and -0.33 (-0.46 to 0.38), respectively (P = 0.85). Ex-preterm adults did not show evidence of increased airway hyperresponsiveness compared with control subjects, 23 and 19%, respectively (P = 0.89). CONCLUSIONS: There are still excess respiratory symptoms 21 years after preterm birth. Reassuringly, this longitudinal study did not show evidence of persistent airway obstruction or airway hyperresponsiveness in ex-preterm adults.

One-year outcomes and health care utilization in survivors of severe acute respiratory syndrome.

BACKGROUND: Severe Acute Respiratory Syndrome (SARS) became a global epidemic in 2003. Comprehensive information on 1-year outcomes and health care utilization is lacking. Research conducted during the SARS outbreak may help inform research planning for future public health emergencies. The objective of this study was to evaluate the 1-year outcomes in survivors of SARS and their family caregivers. METHOD: The study was prospective and observational. We evaluated 117 SARS survivors from Toronto, Ontario. Patients were interviewed and underwent physical examination, pulmonary function testing, chest radiography, a 6-minute-walk test, quality-of-life measures, and self-report of health care utilization. At 1 year, informal caregivers were identified for a survey on caregiver burden. RESULTS: The enrolled survivors of SARS were young (median age, 42 years), and most were women (67%) and health care workers (65%). At 1 year after hospital discharge, pulmonary function measures were in the normal range, but 18% of patients had a significant reduction in distance walked in 6 minutes. The Medical Outcomes Study 36-Item Short Form Health Survey (SF-36) domains were 0.3 to 1.0 SD below normal at 1 year. Of the patients, 17% had not returned to work by 1 year. Fifty-one patients required 668 visits to psychiatry or psychology practitioners. During the SARS epidemic, informal caregivers reported a decline of 1.6 SD below normal on the mental component score of the SF-36. CONCLUSIONS: Most SARS survivors had good physical recovery from their illness, but some patients and their caregivers reported a significant reduction in mental health 1 year later. Strategies to ameliorate the psychological burden of an epidemic on the patient and family caregiver should be considered as part of future pandemic planning.

Detection of age-dependent changes in healthy adult lungs with diffusion-weighted 3He MRI.

RATIONALE AND OBJECTIVES: To investigate changes in lung microstructure in healthy adult subjects with no smoking history using diffusion-weighted 3He MRI. MATERIALS AND METHODS: Diffusion magnetic resonance imaging using hyperpolarized helium 3 (3He) was applied to healthy volunteers to explore the dependence of lung microstructural changes with age, reflected by changes in the apparent diffusion coefficient (ADC) of 3He in lung air spaces. Data from three sites (University of Virginia (UVa), N = 25; University of Wisconsin (UW), N = 8; University of Nottingham (UN), N = 11) were combined in pooled analysis, including a total of N = 44 subjects (age range, 18-69 years; average age, 41.7 +/- 16.7 years). RESULTS: ADC was found to depend on age at all three sites (UW, R = +0.95, P = .0003; UVa, R = +0.74, P < .0001; UN, R = +0.96, P < .0001). Increases in mean ADCs with age appeared similar across sites (UW, +0.0017 cm2 s(-1) y(-1); UVa, +0.0015 cm2 s(-1) y(-1); pooled, +0.0015 cm2 s(-1) y(-1); P = .71). In a regional analysis performed on UW data, the increase in ADC affected all regions of the lung, but the apical and middle regions showed a greater increase compared with the base of the lung. CONCLUSION: Results suggest the observed age dependence of the ADC may be caused by changes in lung microstructure that increase alveolar volume during the aging process.

International Health Links movement expands in the United Kingdom.

The need to strengthen health capacity in developing countries is widely documented. The World Health Organization has called for an increase in the number of health workers in all countries experiencing critical shortages, a significant scaling-up of training and more efficient use of existing health workers. Health Links, long-term mutually beneficial partnerships between UK health institutions and their counterparts in developing countries, are helping to fill these gaps. Links allow for the reciprocal transfer of knowledge and skills between partners, enabling the UK's expertise in health service delivery and training to be channelled towards the needs of those in developing countries, while also bringing a wide range of benefits to the UK. Examples of Health Links in Ethiopia demonstrate such benefits. An increasingly supportive policy environment is enabling a significant expansion in the number of Links. However, the quality of these Links is critical to their impact and thus there is a need both to continue to support those engaging in Links to develop sustainable, mutually beneficial strategic partnerships, and to strengthen the body of evidence of their impacts.

Long-range correlations in rectal temperature fluctuations of healthy infants during maturation.

BACKGROUND: Control of breathing, heart rate, and body temperature are interdependent in infants, where instabilities in thermoregulation can contribute to apneas or even life-threatening events. Identifying abnormalities in thermoregulation is particularly important in the first 6 months of life, where autonomic regulation undergoes critical development. Fluctuations in body temperature have been shown to be sensitive to maturational stage as well as system failure in critically ill patients. We thus aimed to investigate the existence of fractal-like long-range correlations, indicative of temperature control, in night time rectal temperature (T(rec)) patterns in maturing infants. METHODOLOGY/PRINCIPAL FINDINGS: We measured T(rec) fluctuations in infants every 4 weeks from 4 to 20 weeks of age and before and after immunization. Long-range correlations in the temperature series were quantified by the correlation exponent, alpha using detrended fluctuation analysis. The effects of maturation, room temperature, and immunization on the strength of correlation were investigated. We found that T(rec) fluctuations exhibit fractal long-range correlations with a mean (SD) alpha of 1.51 (0.11), indicating that T(rec) is regulated in a highly correlated and hence deterministic manner. A significant increase in alpha with age from 1.42 (0.07) at 4 weeks to 1.58 (0.04) at 20 weeks reflects a change in long-range correlation behavior with maturation towards a smoother and more deterministic temperature regulation, potentially due to the decrease in surface area to body weight ratio in the maturing infant. alpha was not associated with mean room temperature or influenced by immunization CONCLUSIONS: This study shows that the quantification of long-range correlations using alpha derived from detrended fluctuation analysis is an observer-independent tool which can distinguish developmental stages of night time T(rec) pattern in young infants, reflective of maturation of the autonomic system. Detrended fluctuation analysis may prove useful for characterizing thermoregulation in premature and other infants at risk for life-threatening events.

Acinar structure in symptom-free adults by Helium-3 magnetic resonance.

RATIONALE: The apparent diffusion coefficient of hyperpolarized (3)He in the lungs has been shown to correlate directly in animal models with the peripheral airspace size and can detect changes in lung microstructure. OBJECTIVES: To study in vivo the (3)He apparent diffusion coefficient and to demonstrate its sensitivity to changes in lung morphometry as a result of aging, exposure to cigarette smoke, and lung inflation. METHODS: We assessed the variation in the diffusion of hyperpolarized (3)He gas in the lungs by magnetic resonance techniques. Spirometric lung volumes were recorded. MEASUREMENTS: We measured the dependence of (3)He diffusion on age and on reported cigarette smoke exposure in 32 symptom-free adults. We also measured the dependence of the apparent diffusion coefficient on the degree of lung inflation. RESULTS: In healthy never-smokers, the apparent diffusion coefficient increased with age from 0.115 to 0.155 cm(2) . s(-1) at 20 and 70 yr, respectively, increased linearly with lung inflation and was independent of individual's lung size after correcting for age. For active and passive smokers, the apparent diffusion coefficient increased by up to 40% compared with never-smokers with mean values significantly higher (p=0.016 and p=0.0007, respectively). CONCLUSIONS: Peripheral airspace size increases with age and after exposure to smoke in healthy adults in agreement with previous histologic studies. We have confirmed in vivo that peripheral airspace size is independent of intersubject lung size.

Long-term safety of once-daily budesonide in patients with early-onset mild persistent asthma: results of the Inhaled Steroid Treatment as Regular Therapy in Early Asthma (START) study.

BACKGROUND: The Inhaled Steroid Treatment as Regular Therapy in Early Asthma (START) study is a worldwide, randomized, prospective study to investigate early intervention with inhaled corticosteroids in recent-onset mild persistent asthma. OBJECTIVE: To evaluate the safety and tolerability of long-term treatment with once-daily budesonide therapy in patients with mild persistent asthma. METHODS: Patients aged 5 to 66 years with mild persistent asthma for fewer than 2 years and no previous regular corticosteroid treatment received budesonide or placebo once daily for 3 years, in addition to their usual asthma therapy. The daily budesonide dose was 200 microg for children younger than 11 years and 400 microg for those 11 years or older. RESULTS: Overall, 7,221 patients were included in the safety analysis, and a total of 21,520 adverse events were reported (10,850 in the budesonide group and 10,670 in the placebo group). The most commonly reported events included respiratory infections, rhinitis, pharyngitis, bronchitis, viral infections, and sinusitis. The number of deaths and serious adverse events were similar for children and adults in both treatment groups. Fewer asthma-related serious adverse events were reported with budesonide (162) compared with placebo (276). Oral candidiasis was reported more frequently with budesonide (1.2%) than with placebo (0.5%); the frequencies of other adverse effects previously reported to be associated with inhaled corticosteroids (psychiatric disorders, skin disorders, and allergic reactions) were similar. CONCLUSIONS: Three-year treatment with budesonide once daily (200 or 400 microg) is safe and well tolerated in children and adults with newly detected mild persistent asthma.

Peak flow monitoring for guided self-management in childhood asthma: a randomized controlled trial.

We asked whether the addition of PEF recordings to a symptom-based self-management plan improved outcome in school children with asthma. In an open-randomized, parallel-group, controlled trial, we studied children aged 7-14 years with moderate asthma. After a 4-week run-in, 90 children were randomized to receive either PEF plus symptom-based management or symptom-based management alone for 12 weeks. Thresholds for action based on PEF were 70% of best (for increasing inhaled steroids) and 50% of best (for commencing prednisolone). Children were asked to perform twice-daily spirometry at home (using an electronic recording spirometer that revealed only PEF to the study group alone) and to record a symptom diary. The mean daily symptom score was the main outcome. There were no differences between groups in mean symptom score or in spirometric lung function, PEF, quality of life score, or reported use of health services over 12 weeks. During acute episodes, children responded to changes in symptoms by increasing their inhaled steroids at a mean value of PEF of greater than 70% of best so that overall PEF did not contribute to this important self-management decision. Knowledge of PEF did not enhance self-management even during acute exacerbations.