What have the studies shown?

The Leicester pre-school questionnaire translated into Portuguese!

The Leicester pre-school questionnaire has been translated into Portuguese by a team working in Lisbon. Their purpose was twofold; firstly they wanted to find out more about infantile asthma and wheezing in Portugese children below 3 years, and secondly they wanted to standardize methodology to help develop nationwide strategies. Some cultural adaptations to the questions were necessary, but  the repeatability of the questions was good to excellent, similar to the original work. This contributes to the international standardization of methodologies in paediatric respiratory epidemiology.


Tradução com adaptação cultural para portugês e determinação da reprodutibilidade do questionnaire on respiratory symptoms in preschool children.  


Dose lung function change in populations who migrate to a different country?

It has long been recognized that there are variations in lung function between people of different ethnic groups. One possible explanation has been that nutritional or socioeconomic factors are largely responsible for the differences. Some of our previous work in which we compared lung function in children of south Asian origin with that of white children confirmed that white children had generally larger values for lung function, but the differences were not explained by any socioeconomic or cultural factors we were able to measure. There is always the chance, however, that there were socioeconomic factors that we could not measure. If this was the case, then we would expect lung function in successive generations of immigrant populations to gradually approach that of the host country.

We were able to explore this idea by comparing lung function in two groups of south Asian children from the Leicester Cohorts; those whose mothers had been born overseas and immigrated to the UK and those whose mothers had been UK-born. We would expect bigger values of lung function in children of UK-born mothers if lung function in migrants gradually approaches that of the native population. We found that there were no differences in lung function between the two groups of children – if anything, offspring of UK-born mothers had slightly smaller values of lung function.

This was a relatively small study and we would welcome more work in the area. It has important implications because it suggests that differences in lung function are, at least in part, attributable to ethnicity and therefore ethnicity-specific prediction equations may continue to be important, even for populations that have been resident away from their region of origin for more than one generation.


Kuehni CE, Strippoli MF, Spycher BD, Silverman M, Beardsmore CS. (2015) Lung function in the children of immigrant and UK-born south-Asian mothers. Eur Respir J. 2015 Jan 8. pii: ERJ-01521-2014. [Epub ahead of print]


Asthma and Genetics

Asthma tends to run in families, which means that children are more likely to develop asthma if their parents have the condition. This indicates that there is a genetic component to asthma. It is not a single gene effect (such as some types of haemophilia or colour blindness), but many genes are involved. In addition to these genes, environmental influences are necessary for the development of asthma.

Better understanding of which genes contribute to asthma development will help us to predict which individuals are likely to develop the condition, and to better tailor treatment to individuals. Ultimately (though this is some way into the future) we’d like to be able to prevent development of asthma altogether.

This study was led by colleagues from the Departments of Health Sciences and Genetics, University of Leicester and studied the role of the beta-defensin genes (DEFB103, DEFB104 and DEFB4) in the development of asthma and Chronic Obstructive Pulmonary Disease (COPD). We were able to contribute DNA samples from over 600 members of the Leicester Cohorts. The study also included DNA from 1149 adults, some of whom had COPD. We found that the number of copies of the genes was not convincingly linked to the presence of COPD in the adults and although there was some weak evidence of a link to asthma in the children, this needs further research. There was also no association between lung function (measured by blowing tests) and the number of copies of these genes.

Although this study did not find strong links between copy number variation and COPD, asthma, or lung function, it is important to recognise that we have looked at one small piece of the jigsaw that constitutes the genetics of wheeze and asthma, and much more work remains to be done.


Wain LV, Odenthal-Hesse L, Abujaber R, Sayers I, Beardsmore C, et al. (2014) Copy Number Variation of the Beta-Defensin Genes in Europeans: No Supporting Evidence for Association with Lung Function, Chronic Obstructive Pulmonary Disease or Asthma. PLoS ONE 9(1): e84192. doi:10.1371/journal.pone.0084192


Differences in Lung Function Between White and South Asian Children

There are many reports of differences in lung function between people of different ethnic origins. In most of these, white people have been shown to be able to blow out more air, and with more speed, than other people of the same sex, height and age. This is important because predicted values of lung function are usually based on measurements made in white people, which means that when we assess a person from a different ethnic group we run the risk of categorising them as having reduced lung function when, in fact, their measurements are normal for their ethnicity.

Using measurements from children and young people in the cohorts, we set out to see if we also found differences between white and south Asians and, if so, whether we could explain such differences to socioeconomic, environmental or cultural factors, or to differences in asthma, wheezing, or anything relating to birth.  

We studied 1088 white and 275 UK-born south Asian children aged 9-14 years. From their lung function measurements we showed that the white children could blow out more than their south Asian counterparts (i.e. their lungs are about 10% bigger), but that the flows were very similar. This is in line with findings of other groups. Our study was able to show that the differences did not appear to be due to any environmental, social, or cultural factors, nor to differences in the amount of asthma or wheezing. We conclude that the differences are likely to be genetic, and that south Asian children should have their own set of predicted values for lung function.  This contrasts with a general move towards ‘multi-ethnic’ predicted values, and we are continuing to explore this topic in detail.


Strippoli MP, Kuehni CE, Dogaru CM, Spycher BD, McNally T, Silverman M, Beardsmore CS. Etiology of ethnic differences in childhood spirometry. Pediatrics. 2013; doi: 10.1542/peds.2012-3003.


A new and simple tool helps to predict later asthma in preschool children with recurrent wheeze or cough

Many preschool children suffer from wheeze or chronic cough, but not all of them have asthma later. Several tools for improving prediction of later asthma in symptomatic toddlers have been developed. However, some are difficult to use in clinical practice, while other tools have methodological limitations. Our aim was to develop a simple and robust tool for predicting asthma at school-age in symptomatic pre-school children.

We used data from 1-3 year old children, who had visited their doctor for wheeze or recurrent cough. Using information on symptoms at preschool-age, we developed a statistical model to predict presence of asthma 5 years later: Predicting Asthma Risk in Children (PARC). It uses only information which can easily be collected in primary care and is non-invasive (e.g. does not rely on blood tests). PARC has been developed in a standardized way, avoiding methodological limitations of previous instruments such as overfitting.

Of the 1226 preschool children with wheeze or recurrent cough in this study only 345 (28%) had asthma 5 years later. PARC consists of 10 items, which sum up to a maximum score of 15. The items include: gender, age, parental history of asthma, presence of eczema, presence of wheeze apart from colds, of frequent wheeze, of wheeze disturbing daily activity, of wheeze accompanied by shortness of breath and of wheeze triggered by exercise and by inhaled allergens (house dust, pollen or pets).  Despite being so simple, this new tool performs similarly or better compared to previously published instruments.

In summary, the new asthma prediction tool represents a simple, low-cost and non-invasive method to predict the risk for later asthma in symptomatic pre-school children and is ready to be tested in other populations.

Click here to get to our online version of the PARC.


Pescatore AM, Dogaru CM, Duembgen L, Silverman M, Gaillard EA, Spycher BD, Kuehni CE. A simple asthma prediction tool for preschool children with wheeze or cough. Journal of Allergy and Clinical Immunology 2013; doi: 10.1016/j.jaci.2013.06.002.


Breastfeeding is associated with better lung volumes in children of asthmatic mothers 

Prolonged breastfeeding has numerous advantages for infants, mothers and society. The impact of breastfeeding on respiratory health, however, is less clear. While a protective effect against respiratory infections is not disputed, the evidence on breastfeeding and later lung function in the offspring is unclear, especially if the mothers suffer from asthma.
ISPM Bern and University of Leicester analyzed the relationship between breastfeeding and lung function in a sample of 1458 children from the Leicestershire Cohort Studies. Duration of breastfeeding, other exposures and respiratory symptoms were assessed by repeated questionnaires and lung function tests were performed at age 12 years.
The study found that non-breastfed children whose mothers suffered from asthma had lower lung volumes compared to non-breastfed kids of non-asthmatic mothers. However, lung volumes improved if they were breastfed 4 months or longer, approaching values of children whose mothers had no asthma. In all children (independent of maternal asthma), expiratory flows were better if they had been breastfed for 4 months or more.
This study adds importantly to existing evidence against claims that breastfeeding could be harmful in children of asthmatic mothers. It indicates that children of asthmatic mothers benefit particularly from breastfeeding, with improved lung function. The analysis suggests that, rather than acting via reductions of respiratory infections, or prevention of asthma or allergy, breastfeeding might have a direct effect on lung growth. This should be investigated further. In the meantime, breastfeeding is strongly recommended for all infants, including those whose mothers have asthma.


Dogaru CM, Strippoli MP, Spycher BD, Beardsmore CS, Silverman M, Kuehni CE. Breastfeeding and Lung Function at School-Age: Does Maternal Asthma Modify the Effect?
Am J Respir Crit Care Med 2012; doi:10.1164/rccm.201108-1490OC.


New lung alveoli continue to form until at least adolescence

The aim of the lung development study is to investigate the pattern of normal development in children and delineate the factors affecting normal alveolar development. We used a novel technique called hyperpolarized helium-3 magnetic resonance, developed by the university of Nottingham.

We analysed lung alveolar development using this technique and found that new lung alveoli continue to form until at least adolescence (It was previously believed that new alveoli stop forming after 3 years of age).

This is an exciting development, not least because it changes what was taught in textbooks for at least the last 40 years. The potential for new alveolar development beyond age of 3 years implies potential for repair much more than previously believed. However, this also means that the critical period where noxious influences could damage alveolar development is much longer than previously believed.


Narayanan M, Owers-Bradley J, Beardsmore CS, Madam M, Ball I, Garipov R, Panesar K, Kuehni CE, Spycher BD, Williams S, Silverman M.
Alveolarization continues during childhood and adolescence: new evidence from 3He magnetic resonance. 
Am J Respir Crit Care Med 2011; doi:10.1164/rccm.201107-1348OC


Pattern of symptoms in early life is the most useful information for prediction of asthma

Many children experience chesty coughs or wheezing during their first years of life, particularly when they have colds. Although most children outgrow these symptoms as they become older, some go on to develop asthma. But how can one tell whether or not a child will in fact develop asthma? Our team tested how well the Asthma Predictive Index (API, rule for predicting which preschool children are at risk of developing asthma) predicted which of the children in the Leicestershire Cohort Studies developed asthma and compared results with more simple rules based only on the pattern of symptoms the children had in early life.

We found that, although the API worked well in Leicester, the simple rules worked almost as well. These suggest that the most useful information about whether or not a child will develop asthma is contained in the pattern of symptoms they have in early life. Focusing on this information which is easy to obtain and does not require blood samples may lead to improved prediction rules.


Leonardi NA, Spycher BD, Strippoli MPF, Frey U, Silverman M, Kuehni CE.
Validation of the asthma predictive index and comparison with simpler clinical prediction rules. 
J Allergy Clin Immunol 2011;127:1466-1472


Mechanisms underlying allergen- and infection-related wheeze might be independent

Different causes of wheezing episodes, such as infections, exercise or allergens might be indicators of different disease entities underlying childhood wheezing illness. We therefore looked at changes in the prevalence of these causes at different ages (1, 4, 6 and 9 years).

We found that wheezing episodes caused by infection or by both infection and exercise were considerably less reported in older children than in younger ones. In contrast, the proportion of wheezers reporting that episodes were caused by allergens only, allergens and exercise, or all three causes increased by age.

Together with the fact that there was no association between allergen and infection-related causes, this might strengthen the suggestion that viral wheeze and allergen-induced wheeze represent distinct disease entities.


Strippoli MPF, Spycher BD, Pescatore AM, Beardsmore CS, Silverman M, Kuehni CE.
Exclusive viral wheeze and allergic wheeze: evidence for discrete phenotypes
Eur Respir J 2011;38:472-474


Which different kinds of wheezing illness exist?

Many of the children who begin to wheeze in the first few years of their life do not continue to suffer from wheeze as they grow older. Among the children that do suffer from wheeze some have wheeze only when they have a cold while others also have attacks even when they don’t have a cold, for instance, when there is a lot of dust in the air or when they run and play.

Many families have provided detailed information on the symptoms of wheeze and cough that their children experienced since a very young age. By combining the information from different ages we have been able to identify and describe different patterns of wheezing illness in children.


Spycher BD, Silverman M, Brooke AM, Zwahlen M, Kuehni CE.
Distinguishing phenotypes of childhood wheeze and cough: a novel approach with prognosis relevance.
Eur Respir J 2008;31:974-981

Spycher BD, Minder CE, Kuehni CE.
Multivariate modelling of responses to conditional items: New possibilities for latent class analysis.
Stat Med 2009;28:1927-1939

Spycher BD, Silverman M, Kuehni CE. 
Phenotypes of childhood asthma: are they real (review). 
Clin Exp Allergy 2010;40:1130-1141


Childhood immunisations do not increase the frequency of asthma and allergy

Some people have suggested that childhood vaccinations might make children more vulnerable for getting asthma, wheeze and allergies. We have investigated this problem using the Leicester cohorts, by comparing children who got all childhood immunisations with those who didn't. This study showed that there was no increase in asthma in immunised children - in fact fully immunised children may be less likely to develop asthma than children who did not receive all immunisations!


Kuehni CE, Davis A, Brooke AM, Silverman M. 
Vaccinations as risk factors for wheezing disorders.
Lancet 2001;358:1186

Spycher BD, Silverman M, Zwahlen M, Brooke AM, Kuehni CE.
Routine vaccination against pertussis and the risk of childhood asthma: a population-based cohort study. 
Pediatrics 2009;123:944-950

Spycher BD, Silverman M, Kuehni CE.
Timing of routine vaccinations and the risk of childhood asthma.
J Allergy Clin Immunol 2008;122:656


Are wheezing and asthma caused by outdoor air pollution?

We found that troublesome cough is clearly related to levels of air pollution caused by traffic near home, and that pollution might also cause new wheeze in previously healthy children.


Pierse N, Rushton L, Harris RS, Kuehni CE, Silverman M, Grigg J.
Locally-generated particulate pollution and respiratory symptoms in young children.
Thorax 2006;61:216-220

We also showed that it is very important that air pollution is measured accurately, which is done by the Leicester City Council!


Kuehni CE, Strippoli MPF, Zwahlen M, Silverman M.
Association between reported exposure to road traffic and respiratory symptoms in children: evidence of bias.
Int J Epidemiol 2006;35:779-786


Chest problems in south Asian ethnic groups in Leicester

A large proportion of the population of Leicestershire is of south Asian ethnic origin. We know that wheeze and asthma are less common in India, Pakistan and Bangladesh compared to the UK. On the other hand, we see many south Asian children with severe asthma coming to hospital. This is why we wanted to find out what happens to south Asian children whose families have come to live in the UK.

We found that wheezing in schoolchildren is equally common in south Asian and in white children. However, south Asians are more likely to visit their doctor and attend the hospital for wheeze. This might be because they are more likely to have food allergies and to have an allergic and chronic type of asthma.


Kuehni CE, Strippoli MPF, Silverman M.
Food intolerance and wheezing in young south Asian and white children: prevalence and clinical significance.
J Allergy Clin Immunol 2006;118:528-530

While some mothers of the south Asian families taking part in the research were born in the UK, other mothers were born in India, Pakistan, Bangladesh or Africa and have come to the UK at different ages. Our research suggests, that those mothers who were born in the UK or who have immigrated as very young children are at greater risk from developing asthma compared to those who came to the UK at a later age.


Kuehni CE, Strippoli MPF, Low N, Silverman M.
Asthma in young south Asian women in the UK: the importance of early life.
Clin Exp Allergy 2007;37:47-53

This suggests that some aspects of the UK environment cause young children to develop asthma and allergies. Further research may help us to find out and prevent this.


Kuehni CE, Strippoli MPF, Low N, Brooke AM, Silverman M.
Wheeze and asthma prevalence and related health service use in white and south Asian preschool children in the UK.
Clin Exp Allergy 2007;37:1738-1746


Almost 10% of young children snore regularly

Snoring is of increasing concern. Not only does it disturb sleep: in children it can cause various behavioural problems and educational difficulties. We found that only 40% of children aged 1-4 never snore. And, besides the 52% who snore occasionally, be it because of a cold or other short-term problem, no less than 8% snore every night! The proportion of regular snorers rises with age. However, not all children who snore between the ages of one and four will continue to do so; in fact, only 46% of those who snored regularly before their fourth birthday continue to do so when aged between six and nine.


Kuehni CE, Strippoli MPF, Chauliac ES, Silverman M.
Snoring in preschool children: prevalence, severity and risk factors.
Eur Respir J 2008;31:326-333


Are some children missing out?

Even in the modern NHS, the results of the surveys which you have helped us to gather show that diagnosis and treatment of chest problems are less satisfactory in: girls, ethnic minority children and children from poorer parts of the city.


Michel G, Silverman M, Strippoli MPF, Brooke AM, Grigg J, Kuehni CE.
Parental understanding of “wheeze” and its impact on asthma prevalence estimates.
Eur Respir J 2006;28:1124-1130

Chauliac ES, Silverman M, Zwahlen M, Strippoli MPF, Brooke AM, Kuehni CE.
The therapy of preschool wheeze: appropriate and fair?
Pediatr Pulmonol 2006;41:829-838


Answers to questionnaires by parents are very reliable

Some families have filled in several questionnaires for their child. By comparing these, we have found that the information given by parents is very reliable and their memory of earlier illnesses is good.


Kuehni CE, Brooke AM, Silverman M.
Prevalence of wheeze during childhood: retrospective and prospective assessment.
Eur Respir J 2000;16:81-85

Strippoli MPF, Silverman M, Michel G, Kuehni CE.
A parent-completed respiratory questionnaire for one-year olds: repeatability.
Arch Dis Child 2007;92:861-865


Wheezing illness in pre-school children costs the NHS £53m per year

Using data from the Leicester cohort studies, interviews with parents and costs estimates from GPs and hospitals in Leicestershire, we found that wheezing illness in preschool children alone costs the National Health Service (NHS) £53m per year. This includes the costs for medicines, primary care and hospital care.

We need to intensify research to find ways to prevent the development of wheezing in children to save tax-payers money.


Stevens CA, Turner D, Kuehni CE, Couriel JM, Silverman M.
The economic impact of preschool asthma and wheeze.
Eur Respir J 2003;21:1000-1006


Wheezing illness in toddlers became twice as common between 1990 and 1998

In 1990 and again in 1998, we wanted to find out how many young children between the age of one and five years suffered from wheeze.

In 1990, 12% of all parents answered that their children had been wheezing during the past 12 months. This number increased to 26% in 1998. This means that in 1998, one out of four toddlers had breathing problems with wheeze in the past year. Nearly one out of five (19%) needed to take asthma inhalers for treatment. These very important results were published in The Lancet, the best known journal for doctors in Europe!


Kuehni CE, Davis A, Brooke AM, Silverman M.
Are all wheezing disorders in very young (preschool) children increasing in prevalence?
Lancet 2001;357:1821-1825

The aim of the lung development study is to investigate the pattern of normal alveolar development in children and delineate the factors affecting normal alveolar development. We used a novel technique called hyperpolarized helium-3 magnetic resonance, developed by the University of Nottingham.


©  ISPM - University of Bern 2009