Search

There are ethnic differences in lung function, with white subjects having larger height-normalised forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1) than black people or Asians [1, 2]. It has been argued that these differences might be explained by environmental and social factors associated with poverty [3, 4]. Alternatively, the differences in lung volume might be explained by inherent factors, such as genetically determined differences in body frame, with a relatively smaller thoracic cage and, consequently, smaller lungs in some Asian ethnic groups [4, 5]. If the differences were explained mainly or entirely by environmental exposures, lung function in populations migrating from a south-Asian to a western European country should increase in successive generations as standards of living gradually approach those of the host region. Lung function is similarly low in children of migrant and UK-born south-Asian mothers We thank the parents and children of Leicestershire and Rutland, UK, for participating, and Tony Davis (Specialist Community Child Health Services, Leicester City Primary Care Trust, Leicester, UK) for his assistance.

The distinction between episodic viral wheeze (EVW) and multitrigger wheeze (MTW) is used to guide management of preschool wheeze. It has been questioned whether these phenotypes are stable over time. We examined the temporal stability of MTW and EVW in two large population-based cohorts.We classified children from the Avon Longitudinal Study of Parents and Children (n=10 970) and the Leicester Respiratory Cohorts ((LRCs), n=3263) into EVW, MTW and no wheeze at ages 2, 4 and 6 years based on parent-reported symptoms. Using multinomial regression, we estimated relative risk ratios for EVW and MTW at follow-up (no wheeze as reference category) with and without adjusting for wheeze severity.Although large proportions of children with EVW and MTW became asymptomatic, those that continued to wheeze showed a tendency to remain in the same phenotype: among children with MTW at 4 years in the LRCs, the adjusted relative risk ratio was 15.6 (95% CI 8.3–29.2) for MTW (stable phenotype) compared to 7.0 (95% CI 2.6–18.9) for EVW (phenotype switching) at 6 years. The tendency to persist was weaker for EVW and from 2–4 years. Results were similar across cohorts.This suggests that MTW, and to a lesser extent EVW, tend to persist regardless of wheeze severity.

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 years), 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 3-7 years. Collaborators included researchers with access to pulmonary function test data in healthy preschool children. Spirometry centiles were created using the LMS (Lambda-Mu-Sigma) method and extend previously published equations down to 3 years of age. MAIN RESULTS: The Asthma UK centiles charts for spirometry are based on the largest sample of healthy young Caucasian children aged 3-7 years (n=3777) 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 dataset 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 which will facilitate continued updating.

Epidemiological data on snoring from preschool children are scarce, although habitual snoring (snoring on almost all nights) has been associated with poor long-term outcomes. In a population survey of 6,811 children aged 1-4 yrs (from Leicestershire, UK) the present authors determined prevalence, severity and risk factors for snoring, especially habitual snoring. In 59.7% of the children, parents reported snoring in the previous 12 months, including 7.9% with habitual snoring and 0.9% with habitual snoring and sleep disturbance. Prevalence of habitual snoring increased with age from 6.6% in 1-yr-olds to 13.0% in 4-yr-olds. Habitual snoring was associated with: one and both parents smoking (adjusted odds ratio (OR) 1.46 and 2.09, respectively); road traffic (OR 1.23); single parent (OR 1.60); and in White but not South Asian children, socioeconomic deprivation (OR 1.25 and 2.03 for middle and upper thirds of Townsend score, respectively). Respiratory tract symptoms related to atopic disorders and to respiratory infections were strongly associated with snoring; however, body mass index was not. In conclusion, habitual snoring is common in preschool children with one-third of cases attributable to avoidable risk factors. The strong association with atopic disorders, viral infections and environmental exposures suggests a complex aetiology, based on a general vulnerability of the respiratory tract.

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.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.We assessed the variation in the diffusion of hyperpolarized (3)He gas in the lungs by magnetic resonance techniques. Spirometric lung volumes were recorded.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.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).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.

Background: Particulate matter 10 ) from fossil fuel combustion is associated with an increased prevalence of respiratory symptoms in children and adolescents. However, the effect of PM 10 on respiratory symptoms in young children is unclear. Methods: The association between primary PM 10 (particles directly emitted from local sources) and the prevalence and incidence of respiratory symptoms was studied in a random sample cohort of 4400 Leicestershire children aged 1–5 years surveyed in 1998 and again in 2001. Annual exposure to primary PM 10 was calculated for the home address using the Airviro dispersion model and adjusted odds ratios (ORS) and 95% confidence intervals were calculated for each μg/m 3 increase. Results: Exposure to primary PM 10 was associated with the prevalence of cough without a cold in both 1998 and 2001, with adjusted ORs of 1.21 (1.07 to 1.38) and 1.56 (1.32 to 1.84) respectively. For night time cough the ORs were 1.06 (0.94 to 1.19) and 1.25 (1.06 to 1.47), and for current wheeze 0.99 (0.88 to 1.12) and 1.28 (1.04 to 1.58), respectively. There was also an association between primary PM 10 and new onset symptoms. The ORs for incident symptoms were 1.62 (1.31 to 2.00) for cough without a cold and 1.42 (1.02 to 1.97) for wheeze. Conclusion: In young children there was a consistent association between locally generated primary PM 10 and the prevalence and incidence of cough without a cold and the incidence of wheeze which was independent of potential confounders.

The current study aimed to assess prevalence and distribution of use of asthma medication for wheeze in pre-school children in the community. We sent a postal questionnaire to the parents of a random population-based sample of 4,277 UK children aged 1-5 years; 3,410 participated (children of south Asian decent were deliberately over-represented). During the previous 12 months, 18% of the children were reported to have received bronchodilators, 8% inhaled corticosteroids (ICS) and 3% oral corticosteroids. Among current wheezers these proportions were 55%, 25%, and 12%, respectively. Use of ICS increased with reported severity of wheeze, but did not reach 60% even in the most severe category. In contrast, 42% of children receiving ICS reported no or very infrequent recent wheeze. Among children with the episodic viral wheeze phenotype, 17% received ICS compared with 40% among multiple-trigger wheezers. Use of ICS by current wheezers was less common in children of South Asian ethnicity and in girls. Although a high proportion of pre-school children in the community used asthma inhalers, treatment seemed to be insufficiently adjusted to severity or phenotype of wheeze, with relative under-treatment of severe wheeze with ICS, especially in girls and South Asian children, but apparent over-treatment of mild and episodic viral wheeze and chronic cough.

Background Budesonide is the only inhaled corticosteroid to be given a category B pregnancy rating by the US Food and Drug Administration, based on observational data from the Swedish Medical Birth Registry. However, data from large randomized controlled trials are lacking. Objective To compare pregnancy outcomes among patients with recent-onset mild-to-moderate persistent asthma receiving low-dose budesonide vs placebo. Methods In a randomized, double-blind, placebo-controlled trial, 7,241 patients aged 5 to 66 years with mild-to-moderate persistent asthma for less than 2 years and no previous regular corticosteroid therapy received once-daily budesonide or placebo via dry powder inhaler in addition to their usual asthma medication for 3 years. This trial was followed by a 2-year open-label treatment period. The daily dose of budesonide was 400 μg for adults. The study included 2,473 females aged 15 to 50 years at randomization. Pregnancy was not an exclusion criterion (except for US patients). Results Of 319 pregnancies reported, 313 were analyzed. Healthy children were delivered in 81% and 77% of all pregnancies in the budesonide and placebo groups, respectively. Of the 196 pregnancies reported by participants taking budesonide, 38 (19%) had adverse outcomes: 23 (12%) had miscarriages, 3 (2%) had congenital malformations, and 12 (6%) had other outcomes. Of the 117 pregnancies reported in the placebo group, 27 (23%) had adverse outcomes: 11 (9%) had miscarriages, 4 (3%) had congenital malformations, and 12 (10%) had other outcomes. Conclusions Treatment with low-dose inhaled budesonide in females with mild-to-moderate persistent asthma does not seem to affect the outcome of pregnancy.

Background : Studies into the effects of salbutamol in the treatment of wheeze in infancy have been conflicting, possibly due to differences in outcome variables. We aimed to assess the response to salbutamol using indices derived from passive and forced expiration. Methods : We recruited 39 infants who had a history of wheezing (mean age 43 weeks) and measured maximum flow at functional residual capacity (V′maxFRC) by rapid thoracoabdominal compression (RTC), and forced expired volume at 0.4s (FEV 0.4 ) using the raised-volume RTC technique (RV-RTC). We calculated passive compliance ( C rs ), resistance ( R rs ) and time constant ( τ ) from relaxed expirations that followed the augmented inspirations delivered during RV-RTC. Measurements were repeated after aerosol salbutamol (800mcg). Results : Data were obtained in 32 infants for V′maxFRC, 22 for FEV 0.4 and 19 for passive mechanics. There were no mean changes in any index of forced expiration after salbutamol. Some individuals showed significant changes (improvement or worsening) in one or other index. Overall, there was a small increase in C rs after salbutamol but no change in R rs or τ . Conclusions : We found no consistent pattern of response in either index of forced expiration. Validated clinical scores or alternative physiological techniques may be preferable to respiratory mechanics in assessing bronchodilator response.

We measured arterial diameter as a function of generation number (#) in the arteriograms of six postmortem lung preparations from human infants aged 35 to 48 wks post-conceptional age (PCA). The log-log plot of mean diameter as a function of generation number revealed a linear decrease in mean and median diameter with increasing #, which was characterized by its slope alpha and intercept beta (linear regression). The mean arterial diameter per generation as well as the ratio (F) between mother and larger daughter branch and the relative ratio of asymmetry (A) between the larger and the smaller daughter branch was calculated. The values of F(#) and A(#) were found to be constant between 2 and 15 generations in individual lungs which is consistent with the pulmonary arterial tree exhibiting fractal properties. The averaged values (F and A within a subject) of F(#) and A(#) as well as alpha and beta were determined for each lung preparation and found to be constant from 35 to 48 weeks of age, revealing unchanged branching properties in the pre- and postnatal phase of human lung development.

The question "Has your child ever had wheezing or whistling in the chest at any time in the past?" is a simple and widely used proxy measure for the lifetime prevalence of asthma. Our aim was to test its validity in a longitudinal survey, comparing retrospective recall with prospective assessment of lifetime prevalence. A population-based cohort of 1,422 children, surveyed twice previously, was studied again at age 8-13 yrs by postal questionnaire using standardized questions from the International Study of Asthma and Allergies in Childhood (ISAAC). Of those traced (1,190) questionnaires were returned by 89%. The prevalence of current wheeze was higher than in the previous surveys (20.5% versus 12.4% and 12.5%). Reported "wheeze ever" increased significantly from survey 1 (15.6%) to survey 2 (22.4%) and survey 3 (39.2%) and was very similar to the cumulative lifetime prevalence assessed prospectively over three surveys (42.8%). The retrospective question had a good negative predictive value (97%) and a reasonable positive predictive value (65%) compared to prospective assessment. Children reporting "wheeze ever" (but not current wheeze) in surveys 1 and 2 had at survey 3 an asthma prevalence higher than never-wheezers but lower than current-wheezers. It is concluded that retrospective recall of wheeze at age 8-13 yrs is a valid proxy measure for the lifetime prevalence of wheeze.

Respiratory inductive plethysmography (RIP) records movements of the rib cage (RC) and abdomen (AB). A calibration procedure is needed to determine their relative contribution to tidal volume. We evaluated the hypothesis that the relative contribution of the RC and AB could be defined from respiratory efforts made during a brief occlusion of the airways in 10 infants aged 6.5-19 months, who were studied in quiet sleep. Six occlusions were performed during tidal breathing, with and without a pneumotachograph (PNT) and face mask in place. We analyzed the periods of occluded respiratory effort when RC and AB were in opposite directions (paradoxical movements), plotting RC vs. AB and performing a least-squares linear regression to estimate the ratio of the coefficients of AB/RC. Multiple linear regression of AB and RC over tidal volume during about 100 seconds of tidal breathing provided a reference standard. A ratio of 1 means that AB and RC make equal contributions to tidal volume. The feasibility of the occlusion maneuver was poor; only 51% of occlusions with PNT and 54% without led to a paradoxical movement with a good fit (r > 0.9). The mean coefficient of variation (range) was 9.35% (3.9-15.3%) with PNT and 12.1% (2.5%-26.3%) without it. The accuracy was very poor, with the mean AB/RC value being 0.94 with occlusions and 2.39 with multiple linear regression. The mean difference was 1.45 (SD 0.80), yielding 95% confidence limits for the difference of 0.12-3.01. We concluded that, due to its very poor accuracy and feasibility, the occlusion technique is not a useful method to calibrate RIP in infancy.

Respiratory inductive plethysmography (RIP) is a simple technique for an objective, noninvasive assessment of thoracoabdominal asynchrony, which in turn is an indirect measure of airway obstruction. We evaluated different indices of asynchrony obtained by RIP before and after methacholine-induced airway obstruction. Bronchial obstruction was elicited by progressive doubling concentrations of methacholine until a > 15% fall in the transcutaneous oxygen tension (PtcO2) had developed. Maximal expiratory flow rates at functional residual capacity (FRC) (VmaxFRC) was obtained by the squeeze technique before and after the challenge. Fifteen infants with a history of wheezing were studied after sedation. Thoracoabdominal movements were recorded with RIP bands placed around either the upper or the lower ribcage (RC) and around the abdomen (AB). An inspiratory asynchrony index (IAI) and an expiratory asynchrony index (EAI) were calculated as determined by the lag of RC relative to AB at start of inspiration and of expiration, respectively. The total time in asynchrony (TTA: the percentage of time in which the RC and the AB signals were in opposite direction) and phi (an angle derived from a Lissajous loop) were also calculated. All subjects responded to the challenge. The median fall in PtcO2 following methacholine challenge was 23.6% and in VmaxFRC was 43%. A large scatter of baseline values was found for all indices with the exception of TTA. There was no correlation between TTA and age, length, or VmaxFRC. The IAI and EAI with the RC band in the upper position were the most sensitive indices, both within subjects (65% of the subjects had a significant change in IAI and 80% in EAI) and for the group as a whole (median values increased for IAI, P = 0.007, and for EAI, P = 0.017). TTA and phi were less sensitive, and a great discrepancy was observed between the two measurements. Poor results were obtained with the RC band in the lower position. No correlations were found between the changes in IAI and EAI, with the RC band around the lower chest and VmaxFRC. We conclude that IAI and EAI, measured with the RC band in the upper position and another band around the abdomen, can detect changes in thoracoabdominal asynchrony in most infants. The usefulness of assessing IAI and EAI in infants with acute lower airway obstruction needs to be determined.

BACKGROUND--The level of bronchial responsiveness in those with definite asthma correlates with disease severity and markers of airway inflammation. However, in population studies no clear distinction between normal and abnormal is found. Since the outcome of wheeze in early childhood is very variable, a marker of underlying airway inflammation would be of practical value. A stimulus acting indirectly may be more appropriate than one acting directly on smooth muscle. In this study the airway response to a direct (methacholine) and indirect (hypertonic saline) challenge have been compared in 5-6 year old children with past or present wheeze to see if symptom patterns or severity could be distinguished by either test. METHODS--Forty children with a wide spectrum of wheeze were monitored for a six month period after which their pattern and severity of symptoms were graded. Hypertonic saline and methacholine challenges were then performed on separate days. The response was assessed by both respiratory resistance (Rrs6) and transcutaneous oxygen (PTCO2). Atopic status was determined by IgE and skin prick tests. RESULTS--The results of both challenges were similar whether assessed by Rrs6 or PTCO2. There was no difference in the response to either methacholine or saline between different symptom patterns or severity grades, nor was there any correlation with either test to atopic status. CONCLUSIONS--Neither an indirect nor a direct challenge distinguished between past or present wheeze or degree of clinical severity in this group of children. Either wheezy children of this age do not have airway inflammation or bronchial responsiveness is not a marker for it.

The current hypothesis that human pulmonary alveolarization is complete by 3 years is contradicted by new evidence of alveolarization throughout adolescence in mammals. Objectives:We reexamined the current hypothesis using helium 3 (3He) magnetic resonance (MR) to assess alveolar size noninvasively between 7 and 21 years during which lung volume nearly quadruples. If new alveolarization does not occur alveolar size should increase to the same extent. Methods: Lung volumes were measured by spirometry and plethysmography in 109 healthy subjects aged 7 21 years. Using 3HeMR we determined two independent measures of peripheral airspace dimensions: apparent diffusion coefficient (ADC) of 3HeatFRC(n=109)and average diffusion distance of helium (X rms) by q space analysis (n =46). We compared the change in these parameters with lung growth against a model of lung expansion with no new alveolarization. Measurements and Main Results: ADC increased by 0.19 for every 1 increment in FRC (95 confidence interval [CI] 0.13 0.25) whereas the expected change in the absence of neoalveolarization is 0.41 (95 CI 0.31 0.52). Similarly increase of (X rms) with FRC was significantly less than the predicted increase in the absence of neoalveolarization. The number of alveoli is estimated to increase 1.94 fold (95 CI 1.64 2.30) across the age range studied. Conclusions: Our observations are best explained by postulating that the lungs grow partly by neoalveolarization throughout childhood and adolescence. This has important implications: developing lungs have the potential to recover fromearly life insults and respondto emerging alveolar therapies. Conversely drugs diseases or environmental exposures could adversely affect alveolarization throughout childhood. Copyright © 2012 by the American Thoracic Society.

The aim of this study was to compare the fall in transcutaneous oxygen tension (Ptco2) as an outcome measure during bronchial provocation with histamine, with changes in airway function measured by the squeeze technique in healthy infants and those with wheezing disorders. Ptco2 was measured during histamine challenge in 20 infants, aged 6–16 months, of whom 14 had recurrent cough or wheeze (lower respiratory illness, LRI), and 6 were healthy. All were symptom free at the time of testing. The minimum value of Ptco2, after each nebulization was compared with the minimum baseline value. The response to increasing concentrations of histamine was also assessed by measuring maximal flow at functional residual capacity (VmaxFRC) by the squeeze technique. The inhaled concentration of histamine causing a 30% fall in VmaxFRC was calculated to give the provoking concentration (PC30). Baseline VmaxFRC was lower in symptomatic infants (117 mL/s) than the normal infants (322 mL/s; P

Background—Handheld electronic spirometers provide the opportunity for more comprehensive monitoring of lung function at home than has hitherto been available. The aim of this study was to assess the quality of spirometric data collected at home by 90 asthmatic schoolchildren aged 7‐14 years. Methods—After training, children carried out twice daily recordings at home for four consecutive periods of 4 weeks using a data storage spirometer (Vitalograph), encouraged by 4-weekly visits from a research nurse. Compliance (proportion of blows recorded at correct time of day), technical quality (by machine criteria), and valid data recorded (the multiple of compliance and technical ability) were assessed. Results—Mean compliance declined from 81.4% to 70.4% (p

We compared the delivery of a micronized suspension of budesonide by a metered dose inhaler (MDI) with two different spacers (Aerochamber and Aerovent) and by two jet nebulizers (MAD2 and Ultravent) to a ventilated neonatal test-lung using a standard neonatal ventilator circuit. The combination of MDI and Aerochamber was significantly better at delivering budesonide to a filter in front of the test lung (14.2% of aerosolized dose) than were either the MDI and Aerovent (3.6%) or the Ultravent or MAD2 jet nebulizers (0.02% and 0.68% of initial reservoir dose). Of the droplets emerging from the MDI, Aerochamber, and ET tube, 18% of the initial dose was in droplets less than 4.7 microns. Assuming that the test-lung model accurately reflects in vivo deposition, the combination of MDI and Aerochamber appears to be an extremely effective way of delivering budesonide aerosol to ventilated newborn infants.

This study investigated the effect of prolonged rupture of the amniotic membranes (PROM) and probable maternal or fetal sepsis without PROM on the newborn preterm airway. Bronchoalveolar lavage fluid (BALF) was obtained from 38 infants in the first day of life and analyzed for number of white cells and concentration of interleukin-6 (IL-6). The volume of lung epithelial lining fluid (ELF) was estimated using the urea dilution technique. Infants with PROM (n = 13) and those with sepsis (n = 8) had higher total numbers of white cells in BALF compared with infants without PROM or sepsis (n = 17) (55 and 44 versus 7 x 10(4) white cells, p less than 0.01). Uncorrected and urea-corrected IL-6 concentrations were also higher in the two groups (18.5 and 30.8 versus 5.0 fmol/ml BALF, p less than 0.01; 157.7 and 444 versus 88.5 fmol/ml ELF, p less than 0.05). There was a significant correlation between BALF white cells and uncorrected IL-6 concentrations (rs = 0.78, p less than 0.0001). Detectable serum C-reactive protein in newborn infants was associated with increased levels of IL-6 in BALF (42.2 versus 11.8 fmol/ml BALF, p less than 0.05). We conclude that PROM is associated with airway inflammation and raised levels of IL-6 in neonatal lung fluid within the first 24 h of life and that this may initiate a systemic stress response.

This is the authors' final version of the paper published in Amercian Journal of Respiratory and Critical Care, 2009, 179(12), pp. 1079-1080. The definitive version is available at http://ajrccm.atsjournals.org/content/vol179/issue12/index.dtl. DOI: 10.1164/rccm.200904-0567ED

Respiratory resistance (Rrs6), transcutaneous oxygen tension (PtcO2), and oxygen saturation (SaO2) were measured during methacholine challenge in 15 asthmatic children and six normal adults. During bronchoconstriction, induced by a wide range of inhaled methacholine concentrations (0.5-256 g/l), the rise in Rrs6 was reflected by a fall in PtcO2 in all subjects. Although there was a significant mean fall in SaO2 at maximum bronchoconstriction there was no consistent relation between changes in SaO2 and Rrs6. The inhaled dose of methacholine causing a 40% increase in Rrs6 (PD40Rrs6) and a 20% fall in PtCO2 (PD20PtcO2) was calculated for each subject. There was no significant difference in mean PD40Rrs6 and PD20PtcO2, and the relation between the two was similar in the asthmatic children and the normal adults. It was therefore concluded that the measurement of PtcO2, but not SaO2, during methacholine challenge can be used for the assessment of bronchial responsiveness, and that it could prove particularly useful for children too young to cooperate with lung function tests.

The benefits of inhaled therapy in ventilated neonates are recognized, but the reliability of drug delivery in nebulizer-ventilator circuits is uncertain. We quantified the effect of changing variables. Twenty-three freshly killed rabbits (1.15–1.9 kg) were ventilated via a tracheostomy by a pressure-limited, time-cycled ventilator (Neovent). A radioaerosol of 99Tcm pertechnetate from an Ultravent nebulizer (Mallinkrodt) was fed into the proximal ventilator tubing. Two 3-minute nebulizations at “standard settings” were followed by 2 at altered pressure, frequency, gas flow, I:E ratio, or position of the nebulizer in the circuit. Each nebulization was followed by a 3-minute gamma camera image and total deposited radioactivity was measured in excised lungs and trachea. Images demonstrated good peripheral aerosol deposition. At standard settings, lung deposition averaged 2.8% of the aerosol released. This was decreased markedly by reducing tidal volume (ventilator pressures) and residence time of aerosol (I:E ratio). Reduced gas flow decreased deposition slightly, presumably by increased particle size and marginally reduced tidal volume. Deposition did not change with increased frequency; increased minute ventilation was offset by decreased residence time of the aerosol. We conclude that the Ultravent nebulizer can be used to nebulize drugs in a standard neonatal circuit, although the dose delivered is small. Tidal volume and aerosol residence time are important determinants of aerosol delivery. Pediatr Pulmonol 1991; 10:208–213.

There are limited longitudinal data about respiratory morbidity and lung function after preterm birth into adulthood.To determine the evolution of respiratory symptoms, spirometry, and airway hyperresponsiveness of ex-preterm subjects from childhood into adulthood.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.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).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.

Contains fulltext : 69668.pdf (Publisher’s version ) (Closed access) There is poor agreement on definitions of different phenotypes of preschool wheezing disorders. The present Task Force proposes to use the terms episodic (viral) wheeze to describe children who wheeze intermittently and are well between episodes, and multiple-trigger wheeze for children who wheeze both during and outside discrete episodes. Investigations are only needed when in doubt about the diagnosis. Based on the limited evidence available, inhaled short-acting beta(2)-agonists by metered-dose inhaler/spacer combination are recommended for symptomatic relief. Educating parents regarding causative factors and treatment is useful. Exposure to tobacco smoke should be avoided; allergen avoidance may be considered when sensitisation has been established. Maintenance treatment with inhaled corticosteroids is recommended for multiple-trigger wheeze; benefits are often small. Montelukast is recommended for the treatment of episodic (viral) wheeze and can be started when symptoms of a viral cold develop. Given the large overlap in phenotypes, and the fact that patients can move from one phenotype to another, inhaled corticosteroids and montelukast may be considered on a trial basis in almost any preschool child with recurrent wheeze, but should be discontinued if there is no clear clinical benefit. Large well-designed randomised controlled trials with clear descriptions of patients are needed to improve the present recommendations on the treatment of these common syndromes.

In the intricate system of control of airway caliber, the cholinergic (muscarinic) sympathetic nervous system has an important role. Despite the paucity of physiologic or clinical data, it is clear that anticholinergic, antimuscarinic bronchodilator therapy is useful in the management of childhood airway disease. Ipratropium bromide is the only safe and adequately studied agent. It is effective in conjunction with beta-agonists in acute severe childhood asthma and has an important role in the management of wheezy infants and in chronic lung disease of prematurity (bronchopulmonary dysplasia).

Twenty-seven children of very low birthweight (≤1,500 g) whose lung function had been measured on several occasions during the first year were studied at the age of about 9 years. Fifteen of the children had received neonatal intermittent positive pressure ventilation, mostly for respiratory distress syndrome. Ten of the ventilated children were still oxygen dependent at 30 days of age. Compared to the remainder of the group, mechanically ventilated children had reduced lung compliance in early infancy and increased thoracic gas volume in the middle of their first year. These changes correlated with the level of neonatal respiratory therapy as indicated by the oxygen score. Lung compliance in early infancy, but not thoracic gas volume, correlated with forced expiratory volume at 1 second recorded at 9 years. On the other hand, reduced airway conductance showed no significant correlation with the neonatal oxygen score, but there was a strong correlation between airway conductance late in infancy and lung function at 9 years. This relationship was independent of neonatal mechanical ventilation. We conclude that perinatal factors, which may be associated with disturbed lung mechanics early in infancy, are only weak and indirect predictors of childhood lung function. Airway conductance late in infancy, determined by constitutional factors, prematurity itself or other undetermined factors, is a good predictor of airway function at 9 years. Pediatr Pulmonol 1990; 8:74-81.

Contains fulltext : 52933.pdf (Publisher’s version ) (Closed access)

Introduction Early childhood wheeze has been classified according to triggers; exclusive viral wheeze (EVW) and multiple trigger wheeze (MTW). It has been proposed that these phenotypes differ in their aetiology, severity and prognosis. Objectives To examine the prevalence and symptom severity of EVW and MTW in 2–6 year olds. To evaluate the stability of these phenotypes over time, and their association with later wheeze. Method In two longitudinal birth cohorts comprising 18,362 individuals, data on respiratory symptoms were collected at age 2, 4 and 6 years. Parent-reported triggers were used to classify wheeze as EVW or MTW for each 2-year period. Logistic regression analysis was used to estimate odds ratios for current wheeze and relative risk ratios for wheeze phenotypes versus no wheeze, at follow-up compared with baseline. Results At 2 years 17.6% and 22.6% (cohorts 1 and 2 respectively) had wheeze, of which 55.2% and 56.3% had MTW. At 6 years 69.7% and 75.7% of children with wheeze had MTW. Among children with wheeze at baseline, 58–76% with EVW and 46–67% with MTW were in remission 2 years later (cohort 1) and 14–20% and 4–11% (cohort 2). MTW had greater reported symptom-severity at all time-points compared with EVW. When adjusted for symptom-severity, children with EVW at baseline had relative risk ratios (RRR) of 2.9–7.4 and 4.1–15.5 (cohorts 1 and 2 respectively) for EVW and RRR 1.7–2.9 and 1.6–4.0 for MTW at follow-up. Children with MTW at baseline had RRR of 3.1–6.2 in cohort 1 and 3.6–15.6 in cohort 2 for MTW and 1.1–2.7 and 1.4–7.0 respectively for EVW at follow-up. Conclusions When adjusted for symptom severity, wheezing phenotypes based on reported triggers remained stable between 2–6 years of age. Symptom-severity may be a more important determinant than triggers of future wheeze classification in young children.

The epidemiology of wheeze in children, when assessed by questionnaires, is dependent on parents' understanding of the term "wheeze". In a questionnaire survey of a random population sample of 4,236 children aged 6-10 yrs, parents' definition of wheeze was assessed. Predictors of a correct definition were determined and the potential impact of incorrect answers on prevalence estimates from the survey was assessed. Current wheeze was reported by 13.2% of children. Overall, 83.5% of parents correctly identified "whistling or squeaking" as the definition of wheeze; the proportion was higher for parents reporting wheezy children (90.4%). Frequent attacks of reported wheeze (adjusted odds ratio (OR) 3.0), maternal history of asthma (OR 1.5) and maternal education (OR 1.5) were significantly associated with a correct answer, while the converse was found for South Asian ethnicity (OR 0.6), first language not English (OR 0.6) and living in a deprived neighbourhood (OR 0.6). In summary, the present study showed that misunderstanding could lead to an important bias in assessing the prevalence of wheeze, resulting in an underestimation in children from South Asian and deprived family backgrounds. Prevalence estimates for the most severe categories of wheeze might be less affected by this bias and questionnaire surveys on wheeze should incorporate measures of parents' understanding of the term wheeze.

This seventh paper in a review series on different aspects of chronic lung disease following preterm birth focuses on the current knowledge of respiratory symptoms, airway function, airway hyperresponsiveness, and exercise capacity from childhood to adulthood. This paper further considers the long-term implications of these studies for both future research and clinical practice.

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 μg for children younger than 11 years and 400 μg 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 μg) is safe and well tolerated in children and adults with newly detected mild persistent asthma.

We treated a selected group of children attending a difficult asthma clinic with intramuscular triamcinolone acetonide. This study retrospectively reviews markers of asthma severity in those who received one or more monthly doses for three periods: 1) 3 months preceding the first injection (pretreatment), 2) from the first injection to 1 month after the last injection (treatment period), and 3) 3 months after the treatment period (follow-up period). Severity markers during the treatment and follow-up periods were compared with the pretreatment period by paired t-test. Five children (5-13 years old) received a single dose, and 8 children (12-15 years old) received multiple doses. Multiple doses of triamcinolone (n = 3-5) were associated with a fall in the number of asthma exacerbations (P < 0.01) and hospital admissions (P < 0.01) in both the treatment and follow-up periods. A single dose reduced exacerbations (P < 0.05, treatment vs. pretreatment) but not hospital admissions. We conclude that intramuscular triamcinolone is a useful short-term therapy in difficult asthma. Whether its efficacy is due to improved compliance, or an improved anti-inflammatory profile compared with oral steroids, remains unclear.

As little is known about the natural history of bronchial responsiveness and the development of wheezing symptoms in early childhood, a cohort of children at risk of allergy, whose lung function and bronchial responsiveness had been measured in the neonatal period, was followed prospectively for 10 (SD, 0.8) years in order to determine the role of neonatal measurements on wheezing history and later lung function. A potential role for beta-2 adrenoceptor (β2AR) polymorphisms in these relationships was also sought as a secondary objective. Of the original 73 children, wheezing history was available in 65 (89%), and 49 (67%) attended the laboratory for physiological measurements and genotyping of β2AR. Wheezing was categorized as occurring 1) only before the fourth birthday, 2) after the fourth birthday, or 3) never. No relation was seen between neonatal and later lung function. However, neonatal bronchial responsiveness predicted subsequent FEV1 (P = 0.03). Increased neonatal bronchial responsiveness was associated with transient wheeze

The effect of prophylactic nasal corticosteroids on wheezing episodes associated with colds was investigated in a 12 week parallel group, double blind, randomised controlled trial in preschool children.Data were collected from 50 children aged 12-54 months with a history of at least three episodes of wheeze associated with colds over the previous winter, but few or no interval symptoms; 24 were given one dose of fluticasone aqueous nasal spray (50 micro g) into each nostril twice daily and 26 received an indistinguishable placebo spray. Episodes of lower respiratory illness occurring within 2 days of the onset of a cold were identified from daily symptom diaries. The main outcome was nocturnal symptom score during the first 7 days of an episode.The groups were well balanced on entry except that the treatment group had a history of more prolonged episodes. During the trial there was no significant difference in the number of episodes in the treatment and control groups (27 and 37, respectively), in the severity of nocturnal symptoms (mean score 1.33 and 1.22, respectively, confidence interval of difference -0.24 to +0.47) or in daytime symptoms, activity or total scores during episodes. Compliance was estimated to be over 50% in 43 of the children.Nasal corticosteroid treatment does not prevent acute wheezy episodes associated with upper respiratory infections (common colds) in preschool children.

It has been shown that inflammatory cells in the newborn lung are fetal in origin, whereas those in the amniotic fluid are maternal. In order to explore the relationship between fetal amnionitis and neonatal pneumonitis, we collected paired samples of gastric aspirate within 2 hours of birth, and bronchoalveolar lavage fluid within 24 hours of birth from intubated preterm infants. Leukocyte counts in bronchoalveolar lavage fluid correlated with the duration of membrane rupture (r = 0.68, P = 0.0001). There was a high degree of correlation between leukocyte counts in the two fluids (r = 0.86, P = 0.0001). The factors responsible for this association are unknown. Pediatr Pulmonol. 1993; 16:59–61. © 1993 Wiley-Liss, Inc.

Episodic wheezing associated with viral infections of the upper respiratory tract (URT) is a common problem in young children but also occurs in adults. It is hypothesized that an experimental infection with human coronavirus (HCoV), the second most prevalent common cold virus, would cause lower respiratory tract (LRT) changes in adults with a history of viral wheeze.Twenty-four viral wheezers (15 atopic) and 19 controls (seven atopic) were inoculated with HCoV 229E and monitored for the development of symptoms, changes in airway physiology and provocative concentration of methacholine causing a 20% fall in forced expiratory volume in one second (FEV1) (PC20). At baseline, viral wheezers were similar to controls in PC20(mean±sd log2PC20: 5.1±1.9 and 5.8±1.4 g·L−1, respectively) but had a lower FEV1than controls (mean±sd 85.8±11.4 and 95.6±13.2% predicted, respectively p1and peak expiratory flow on days with LRT symptoms (days 3–6), but a progressive reduction in PC20from baseline on days 2, 4 and 17 after inoculation (by 0.82, 1.35 and 1.82 doubling concentrations, respectively). The fall in PC20affected both atopic and nonatopic subjects equally. There were no changes in FEV1or PC20in controls.An adult model of viral wheeze that is independent of atopy and therefore, of classical atopic asthma was established.

Background—The collection of induced sputum provides a non-invasive method of investigating airway inflammation. Few studies have been performed in children, so a study was undertaken to determine the feasibility of sputum induction, the repeatability of eosinophil counts and sputum eosinophil cationic protein (ECP) levels, and the relation of these to current asthma severity. For comparison, serum ECP levels were also measured. Methods—In a cross sectional study of children aged 5‐15 years, 27 healthy children and 60 with asthma underwent sputum induction using inhaled nebulised hypertonic saline. The whole sputum sample was used for analysis. Ten children with stable asthma repeated the procedure within 10 days. Results—A satisfactory sample (>500 non-squamous cells) was obtained in 61% of children with asthma and in 60% of healthy controls. The limits of agreement within subjects ranged from a 0.68 to 2.8 fold diVerence for eosinophil diVerential counts and from 0.38 to 4.4 fold for sputum ECP. Despite a median of 42% squamous cells, significant diVerences were found between asthma and healthy controls for the eosinophil diVerential count (p = 0.0004), total eosinophil counts (p = 0.03), and sputum ECP level (p = 0.0001). Overall, there was no correlation between any marker of airway inflammation and asthma severity, however expressed, including lung function. Conclusions—Sputum induction is only possible in a proportion of children. The repeatability of sputum cell counts and ECP levels, measured in a small number of children, was similar to that reported in adults. Sputum analysis revealed no evidence of airway inflammation in a number of highly symptomatic children with asthma. (Thorax 2000;55:768‐774)

Among the tidal expiratory flow measurements that have been suggested as surrogate tests for airway obstruction, a short time to reach peak tidal expiratory flow (tpef) is the most widely used. Time to peak expiratory flow is most often expressed as the ratio between tpef and total expiratory time (te). As te strictly depends inversely on respiratory rate (RR), we studied the hypothesis that an increase in RR (and a fall in te) with the development of airway obstruction during methacholine or histamine challenge in infants could mask a decrease of tpef when expressed as tpef/te. Thirty-three infants (ages 6.5–23 months) with recurrent wheeze were studied during sedated sleep. Runs of tidal breathing and maximal expiratory flow at FRC (˙VmaxFRC) measured by the squeeze technique were obtained before and after the challenge. All infants responded to the challenge: the median fall in PcO2 was 25%, and it was 43% in ˙VmaxFRC. RR increased from a median value of 31.1 to a median of 35.1 breaths/min. Both tpef and te were significantly shorter after the challenge (P < 0.001 and 0.004, respectively); however, the decrease in tpef/te was not significant (P = 0.081). The change in tpef/te was positively correlated with the change in RR (r = 0.51, P = 0.003). To analyze better the effect of changes in RR on various indices, we divided the patients into two groups: in 17 subjects with a small increase in RR (

The aim of this randomized, double-blind, placebo-controlled trial was to assess the short-term effect of a topical glucocorticoid (budesonide 600 μg twice daily) vs. placebo administered by metered dose inhaler (MDI) and spacer (Aerochamber MV15) directly into the endotracheal tube of intubated infants for 7 days. Twenty preterm infants (mean birthweight, 1,030 g; mean gestational age, 27.3 weeks) who still needed assisted ventilation at 14 days of age were randomly assigned to receive budesonide (n = 9) or placebo (n = 11) and completed the study. The primary outcome was the need for mechanical ventilation after 7 days of treatment. Other outcome variables included ventilator settings, blood gases, serum cortisol levels, and bronchoalveolar lavage inflammatory cell counts. No ventilated infant was extubated during the study period. The treatment group showed significant improvements in mean peak inspiratory pressure, ventilator efficiency index, and (A-a) oxygen difference. There were no changes in the placebo group. Serum cortisol levels and bronchoalveolar lavage cell counts did not change significantly during the study period. There was no difference in side effects between the groups. This trial demonstrates that topical budesonide administered by MDI and Aerochamber produces clinical improvement in ventilated preterm infants, without glucocorticoid side effects. Pediatr Pulmonol. 1996; 21:231–235. © 1996 Wiley-Liss, Inc.

The interrupter technique is a noninvasive method for measuring airway resistance during quiet breathing which requires minimal subject cooperation. It, therefore, has enormous potential for use in young children unable to cooperate with conventional lung function tests. We evaluated the interrupter technique during bronchial challenge with methacholine administered by the tidal breathing method in 10 5-year-old asthmatic children. The mouth pressure/time [P mo(t)] curve obtained following brief airflow interruption during the expiratory phase of quiet breathing was analyzed to determine the interrupter resistance (Rint) using four different methods: RintC, a smooth curve fit with back-extrapolation; RintEO, calculated from the pressure change after the postinterruption oscillations had decayed (end-oscillation); RintL, two-point linear fit with back-extrapolation; and RintEI, calculated from the pressure change at the end of the period of interruption. The four Rint methods were compared for repeatability and sensitivity with the direct measurement of resistance by the forced oscillation technique (Rrs), and with an independent method of measuring the response to challenge, utilizing the change in transcutaneous oxygen tension (PtcO2). The sensitivity of the methods was defined by a sensitivity index (SI), the change after challenge expressed in multiples of the baseline standard deviation. The PtcO2 method had the lowest variability and was by far the most sensitive method (geometric mean SI 18.9), at least 1 doubling concentration more sensitive than the other techniques in every subject (P < 0.05). RintL was more sensitive than the other interrupter methods (geometric mean SI: RintL 4.2; RintC 1.0; RintEO 2.7; RintEI 3.1; P < 0.05) and similar in sensitivity to Rrs (geometric mean SI 4.6) in 7 out of 10 children in which this could be measured. We conclude that the interrupter method provides a simpler method than the oscillation technique for assessing airway obstruction in this age group.

Patterns of tidal respiratory flow have been shown to relate well to airway function in adults, and one epidemiological study in infants has demonstrated the value of the ratio of time to reach peak tidal expiratory flow to the total expiratory time (tpef/te) in predicting subsequent wheezing. The aim of this study was to evaluate tpef/te as a measure of lung function, by sequential observations over the first year, on a group of 22 healthy infants and on 32 infants with a history of mild recurrent lower respiratory illness (LRI), and by single observations on 20 infants with asthma and 20 with severe chronic lung disease of prematurity. We compared tpef/te measured in quiet, supine sleep (under sedation) through a face mask and pneumotachograph, with a measure of airway function, maximal flow at functional residual capacity (VmaxFRC), obtained from partial forced expiratory flow volume loops using the “squeeze” technique. In healthy infants tpef/te was significantly longer at 1 month than at 6 months (median values, 0.38 (95% CI, 0.3M.43) and 0.28 (95% CI, 0.26–0.33), respectively). Between 6 and 12 months tpef/te did not alter significantly and it was independent of VmaxFRC. Both tpef and te as well as their ratio varied with frequency of breathing over the first year of life, but not within each individual age band, due to the narrow spread of frequencies at each age. In assessing airway obstruction, tpef/te was less sensitive than VmaxFRC. There was no difference between healthy infants, those with LRI, and infants with asthma. Values outside the 95% CI for our control group of healthy infants were only seen in the group of infants with severe chronic lung disease of prematurity (median value, 0.16; 95% CI, 0.12–0.22), most of whom demonstrated expiratory flow limitation during tidal breathing. We found the tidal breathing index tpef/te to be an insensitive measure of airway function in infants, compared with VmaxFRC. Pediatr Pulmonol. 1994; 17:285–290. © 1994 Wiley-Liss, Inc.

Tidal breathing indices have been used to assess histamine-induced airway obstruction in adults and children. The aim of this study was to see whether they could be used to assess histamine challenge in infants. Tidal flow during quiet breathing was measured using a face mask and pneumotachograph and maximum flow at functional residual capacity (VmaxFRC) was measured from partial forced expirations in 18 sleeping, sedated infants who responded to histamine challenge and in 18 nonresponders. The tidal indices calculated were inspiratory and expiratory time (ti and te), tidal peak expiratory flow (PEF), mean tidal expiratory flow rate (VT/te) and the expiratory time constant of the respiratory system (trs). The time to maximal expiration divided by expiratory time (tme/te) and 2 revised forms of this index (tme(a)/te and tme(b)/te) were also calculated. Recordings of tme(a) and tme(b) were taken at 95% of peak tidal expiratory flow, before and after the peak, respectively. In nonresponders, there was an insignificant mean rise in VmaxFRC of 11.8% but no change in any tidal index. In responders, the mean percentage fall in VmaxFRC was 43.3% (range, -31 to -81%); trs fell from 0.61 s to 0.51 s (P < 0.05) and breathing frequency and mean tidal expiratory flow rate increased from 34.0 to 37.5 min-1 (P < 0.01) and from 66.6 to 72.6 mL.s-1 (P < 0.05), respectively, suggesting that infants had adopted a strategy of active expiration in response to bronchial challenge. There was no change either in tme/te or in the revised indices after challenge.(ABSTRACT TRUNCATED AT 250 WORDS)

BACKGROUND: The airway response to bronchial provocation may be evaluated by monitoring the fall in transcutaneous oxygen tension (PtcO2) but the repeatability of this method has not been rigorously assessed. METHODS: To determine the repeatability of this indirect method of assessment, bronchial challenge was performed with methacholine in nine children with stable asthma (age range 6-12 years) and was repeated 24 hours later. The response was determined by the fall both in forced expiratory volume in one second (FEV1) and in PtcO2. A modified tidal inhalation protocol was used in which quadrupling concentrations of methacholine were given, thereby reducing the time taken for the full challenge by almost half. The concentrations of methacholine that provoked a 20% decrease in FEV1 (PC20FEV1) and 15% and 10% falls in PtcO2 (PC15PtcO2, PC10PtcO2) were calculated. RESULTS: Repeatability measures, assessed as the 95% range for a single determination, were +/- 0.96 and +/- 1.12 doubling concentration differences respectively for PC15PtcO2 and PC10PtcO2 and +/- 0.80 for PC20FEV1. CONCLUSION: This challenge method using quadrupling concentrations and an indirect assessment of the response by PtcO2 was sufficiently repeatable for clinical use and compared favourably with repeated challenge assessed by FEV1. The PtcO2 method is simple and effort independent, and should prove particularly useful for measuring bronchial reactivity in young children.

There can no longer be any doubt that, within the spectrum On this dubious basis, a third phenotype with a peak prevalence at six years was identified between the group of of wheezing disorders of childhood, several distinct phenoearly transient wheezers and later atopic asthmatic subjects. types can be recognised. Although clinicians have been The distinction between children who wheezed in the first aware of this for decades, it is only through the painstaking three years and those who only wheezed in their sixth year recording and analysis of population cohorts over many is dependent simply on the time points which were chosen years that convincing evidence has emerged. by the Tucson group. Bearing in mind the continual switchIt is worth reminding ourselves here of three important ing which occurs between the wheezing and non-wheezing issues in long term studies of the natural history of disease. sets in a population over the years, a full breakdown of Firstly, studies which set out to test explicit hypotheses are the groups would be needed to make a judgement on the especially important. Although valuable information can numbers of phenotypes. Our own estimate from tables 3 be gleaned from massive information gathering projects, and 4 shows that atopy (by skin prick tests at the age of this is often more by luck than design. Secondly, a long 11) was about 60% in currently non-wheezing children at term approach to organisation and funding is needed to all ages, while the proportion of atopic children in the ensure the best gains from early investment. We detect a wheezing groups rose steadily from 71% at three years of reluctance to plan far ahead in the UK, perhaps driven age to 76% of those wheezing at six years and to 90% at by the four yearly research assessment exercises in UK age 11. This suggests a steady enrichment of atopic children universities and by project grants of 2–3 years duration. within (or a loss of non-atopic children from) the declining Thirdly, data must be stored in an accessible format. wheezing population. A further phenotype perhaps? Written records are bulky but they are durable and reRather than force each child into a particular phenotype, trievable over long periods. With advances in technology, is it not more useful and logical to consider the risk factors will electronic archives be equally accessible in 60 years which may be operating over different time periods in time, or will the decipherment of Linear B be re-enacted the population, and to which individual children may be each time we try to analyse old data sets? variously susceptible? 11 Figure 1 (adapted from WenPapers in this issue of Thorax from two of the most nergren and Wilson) is an attempt to illustrate this point. influential recent cohort study groups – from Aberdeen, The implications are that clinical phenotypes are not static Scotland and Tucson, USA – address the subject of so that transient viral wheeze can, for instance, occur in childhood wheezing phenotypes, their classification and subsequently atopic wheezers. The cohort data can then be heredity. 3 While neither provides unambiguous results, used to examine questions relating to interactions between both have important messages, methodological lessons, these risk factors. and interesting data. It is important to subject them to The latest instalment concerning the highly informative public scrutiny and debate. What can we make of them? Aberdeen cohort 13 14 considers their offspring 30 years The Tucson cohort is younger but has the advantage of after recruitment. Attrition, small and highly selected detailed information collected during early childhood – an study groups, and statistically marginal outcomes present age when many formative events occur, when the rate of problems. For example, the conclusions that prepubertal developmental change is at its greatest, and when wheezing male non-atopic offspring of probands with a childhood phenotypes are changing. The original Aberdeen cohort history of wheezy bronchitis have smaller spirometric values was recruited 30 years ago from children aged 10–14 years, than controls, and that these children are less likely to the age at which the (current) Tucson data end. It is suffer current (but not past) wheeze than the children tempting – despite a generation time gap and 5000 miles of non-atopic controls, is based on tiny numbers and – to treat them as providing a continuous account. This could be rash. The report by Stein and colleagues from Tucson deals with clinical features of the 60% of the original birth cohort still living in the area at age 11, complementing data collected at birth, three years and six years. These data points arbitrarily divide childhood into age periods and we need to remind ourselves that changes occur gradually during childhood, not at fixed time points. A comprehensive set of clinical and physiological data was collected. The population may be atypical in that, at 11, 25% had a current history of wheezing and 60% were atopic on skin prick testing. Methacholine responsiveness, positive skin tests, and male sex were strongly linked with current wheeze at 11, but not with wheeze at younger ages. Again, this confirms previous observations in high risk populations. In contrast to other studies which found PEF Birth