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1.  Home environment and severe asthma in adolescence: a population based case-control study. 
BMJ : British Medical Journal  1995;311(7012):1053-1056.
OBJECTIVE--To investigate the effects of the home environment on the risk of severe asthma during adolescence. DESIGN--A questionnaire based case-control study drawn from a cross sectional survey of allergic diseases among secondary school pupils in Sheffield in 1991. SUBJECTS--763 children whose parents had reported that over the previous 12 months they had suffered either 12 or more wheezing attacks or a speech limiting attack of wheeze. A further 763 children were frequency matched for age and school class to act as controls. Analysis was restricted to 486 affected children and 475 others born between 1975 and 1980 who had lived at their present address for more than three years. RESULTS--Independent associations with severe wheeze were seen for non-feather bedding, especially foam pillows (odds ratio 2.78; 95% confidence interval 1.89 to 4.17), and the ownership of furry pets now (1.51; 1.04 to 2.20) and at birth (1.70; 1.20 to 2.40). These estimates were derived from subjects whose parents denied making changes in the bedroom or avoiding having a pet because of allergy. Parental smoking, use of gas for cooking, age of mattress, and mould growth in the child's bedroom were not significantly associated with wheezing. CONCLUSIONS--Either our study questionnaire failed to detect the avoidance or removal of feather bedding by allergic families or there is some undetermined hazard related to foam pillows. Synthetic bedding and furry pets were both widespread in this population and may represent remediable causes of childhood asthma.
PMCID: PMC2551362  PMID: 7580660
2.  Primary prevention of asthma and atopy during childhood by allergen avoidance in infancy: a randomised controlled study 
Thorax  2003;58(6):489-493.
Background: Recent increases in the prevalence of asthma and atopy emphasise the need for devising effective methods for primary prevention in children at high risk of atopy.
Method: A birth cohort of genetically at risk infants was recruited in 1990 to a randomised controlled study. Allergen avoidance measures were instituted from birth in the prophylactic group (n=58). Infants were either breast fed with mother on a low allergen diet or given an extensively hydrolysed formula. Exposure to house dust mite was reduced by the use of an acaricide and mattress covers. The control group (n=62) followed standard advice as normally given by the health visitors. At age 8, all 120 children completed a questionnaire and 110 (92%) had all assessments (skin prick test, spirometry, and bronchial challenges).
Results: In the prophylactic group eight children (13.8%) had current wheeze compared with 17 (27.4%) in the control group (p=0.08). Respective figures were eight (13.8%) and 20 (32.3%) for nocturnal cough (p=0.02) and 11 of 55 (20.0%) and 29 of 62 (46.8%) for atopy (p=0.003). After adjusting for confounding variables, the prophylactic group was found to be at a significantly reduced risk for current wheeze (odds ratio (OR) 0.26 (95% confidence interval (CI) 0.07 to 0.96)), nocturnal cough (OR 0.22 (95% CI 0.06 to 0.83)), asthma as defined by wheeze and bronchial hyperresponsiveness (OR 0.11 (95% CI 0.01 to 1.02)), and atopy (OR 0.21 (95% CI 0.07 to 0.62)).
Conclusion: Strict allergen avoidance in infancy in high risk children reduces the development of allergic sensitisation to house dust mite. Our results suggest that this may prevent some cases of childhood asthma.
doi:10.1136/thorax.58.6.489
PMCID: PMC1746711  PMID: 12775858
3.  The home environment and asthma symptoms in childhood: two population based case-control studies 13 years apart 
Thorax  1997;52(7):618-624.
BACKGROUND: Prevalence surveys of asthma and/or wheezing among all children aged between 7 1/2 and 8 1/2 attending state and private schools in the London Borough of Croydon were conducted in February 1978 and February 1991. Two population based case-control studies drawn from the survey responders were used to investigate the association between childhood wheeze and characteristics of the home environment and to assess whether changes in these characteristics between 1978 and 1991 may have contributed to an increase in the population prevalence of wheeze among school children. METHODS: Information on exposure to potential indoor environmental risk factors was obtained from parents by home interview and compared between cases-that is, children with frequent (> or = 5) or in-frequent (1-4) attacks of asthma or wheezing in the past 12 months- and controls, with adjustment for study. Changes in exposure over time were assessed by comparing control groups. RESULTS: Between 1978 and 1991 the population prevalence odds of wheeze increased by 20% (OR 1.20; 95% CI 1.04 to 1.39). Change in parental smoking, gas cooking, pet ownership, and central heating did not appear to explain the rise. Use of non-feather pillows was positively associated with childhood wheeze even after adjusting for other risk factors and after re-coding from non-feather to feather cases thought to have changed pillow in response to symptoms (OR 1.54; 95% CI 1.13 to 2.10). The proportion of control children reportedly using non-feather pillows was 44% in 1978 and 67% in 1991. CONCLUSIONS: Increased use of non-feather pillows was the only domestic indoor exposure studied which appeared to explain a modest rise in prevalence of wheeze from 1978 to 1991. Our analysis attempts to address behavioural change in response to the child's symptoms but an artifact arising from lifelong avoidance of feather bedding in atopic families cannot be entirely discounted. 



PMCID: PMC1758604  PMID: 9246133
4.  Asthma and other wheezing disorders in children 
BMJ Clinical Evidence  2006;2006:0302.
Introduction
Asthma is more common in children with a personal or family history of atopy, increased severity and frequency of wheezing episodes, and presence of variable airway obstruction or bronchial hyperresponsiveness. Precipitating factors for symptoms and acute episodes include infection, house dust mites, allergens from pet animals, exposure to tobacco smoke, and anxiety.
Methods and outcomes
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of treatments for acute asthma in children? What are the effects of single-agent prophylaxis in children taking as-needed inhaled beta agonists for asthma? What are the effects of additional prophylactic treatments in childhood asthma inadequately controlled by standard-dose inhaled corticosteroids? What are the effects of treatments and of prophylactic treatments for acute wheezing in infants? We searched: Medline, Embase, The Cochrane Library and other important databases up to October 2005 (BMJ Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
Results
We found 84 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
Conclusions
In this systematic review we present information relating to the effectiveness and safety of the following interventions: beta2 agonists (high-dose nebulised, long-acting [inhaled salmeterol], short-acting [oral salbutamol or by nebuliser, or metered-dose inhaler/spacer versus nebuliser]), corticosteroids (oral prednisolone, systemic, inhaled higher or lower doses [beclometasone]), ipratropium bromide (single or multiple dose inhaled), leukotriene receptor antagonists (oral montelukast), nedocromil (inhaled), oxygen, sodium cromoglycate (inhaled), or theophylline (oral or intravenous).
Key Points
Childhood asthma can be difficult to distinguish from viral wheeze and can affect up to 20% of children.
The consensus is that oxygen, high dose nebulised beta2 agonists and systemic corticosteroids should be used to treat an acute asthma attack. High dose beta2 agonists may be equally effective when given intermittently or continuously via a nebuliser, or from a metered dose inhaler using a spacer, in children with an acute asthma attack.Admission to hospital may be averted by adding ipratropium bromide to beta2 agonists, or by using high dose nebulised or oral corticosteroids.
Prophylactic inhaled corticosteroids improve symptoms and lung function in children with asthma. Their effect on final adult height is unclear. Inhaled nedocromil, inhaled long acting beta2 agonists, oral theophylline and oral leukotriene receptor antagonists are less effective than corticosteroids.Inhaled sodium cromoglycate does not seem to improve symptoms.
CAUTION: Monotherapy with long acting beta2 agonists reduces the frequency of asthma episodes, but may increase the chance of severe asthma episodes and death when those episodes occur. Intravenous theophylline may improve lung function in children with severe asthma, but can cause cardiac arrhythmias and convulsions.
We don't know whether adding higher doses of corticosteroids, long acting beta2 agonists, oral leukotriene receptor antagonists or oral theophylline to standard treatment improves symptoms or lung function in children with uncontrolled asthma.
In infants with acute wheeze, short acting beta2 agonists via a nebuliser or a spacer may improve symptoms, but we don't know whether high dose inhaled or oral corticosteroids or inhaled ipratropium bromide are beneficial.
Oral short acting beta2 agonists and inhaled high dose corticosteroids may prevent or improve wheeze in infants but can cause adverse effects. We don't know whether lower dose inhaled or oral corticosteroids, inhaled ipratropium bromide or inhaled short acting beta2 agonists improve wheezing episodes in infants.
PMCID: PMC2907635
5.  Sensitivity to Five Types of House Dust Mite in a Group of Allergic Egyptian Children 
Background: The published data on house dust mite (HDM) sensitization from Egypt are scanty. We sought to investigate the sensitization to five different types of HDM among a group of allergic children in a trial to outline the most frequent sensitizing strains in the Cairo Province.
Methods: We consecutively enrolled 100 asthmatic patients, aged 1–7 years, of whom 22 had concomitant skin allergy. Skin prick testing was performed using allergen extracts of Dermatophagoides pteronyssinus, Dermatophagoides farinae, Lepidoglyphus destructor, Tyrophagus putrescentiae, and Acarus siro.
Results: Twenty-four patients (24%) were sensitized to one or more strains of HDM. Sensitization to one strain was revealed in 12% of the studied sample, while sensitization to two or three strains was detected in 8% and 4% respectively. Twelve percent of the enrolled children were sensitive to D. pteronyssinus, 11% to D. farinae, 7% to L. destructor, 6% to T. putrescentiae, and 4% to A. siro. Eight out of the 12 (66%) children sensitive to one strain had mild intermittent asthma, while five out of eight (62.5%) sensitive to two strains had moderate persistent asthma. All children sensitized to three strains of HDM had persistent rather than intermittent asthma. HDM sensitization did not correlate significantly to the history of sun exposure, bed mattresses and pillows, living in farms, or exposure to stored grains. The co-existence of atopic dermatitis tended to have a higher rate of HDM sensitization.
Conclusion: D. pteronyssinus and D. farinae represent the most common sensitizing strains in the studied sample. Wider-scale population-based studies are needed to assess the prevalence of HDM allergy and its clinical correlates in our country.
doi:10.1089/ped.2014.0333
PMCID: PMC4171383  PMID: 25276487
6.  House dust mite barrier bedding for childhood asthma: randomised placebo controlled trial in primary care [ISRCTN63308372] 
BMC Family Practice  2002;3:12.
Background
The house dust mite is the most important environmental allergen implicated in the aetiology of childhood asthma in the UK. Dust mite barrier bedding is relatively inexpensive, convenient to use, and of proven effectiveness in reducing mattress house dust mite load, but no studies have evaluated its clinical effectiveness in the control of childhood asthma when dispensed in primary care. We therefore aimed to evaluate the effectiveness of house dust mite barrier bedding in children with asthma treated in primary care.
Methods
Pragmatic, randomised, double-blind, placebo controlled trial conducted in eight family practices in England. Forty-seven children aged 5 to 14 years with confirmed house dust mite sensitive asthma were randomised to receive six months treatment with either house dust mite barrier or placebo bedding. Peak expiratory flow was the main outcome measure of interest; secondary outcome measures included asthma symptom scores and asthma medication usage.
Results
No difference was noted in mean monthly peak expiratory flow, asthma symptom score, medication usage or asthma consultations, between children who received active bedding and those who received placebo bedding.
Conclusions
Treating house dust mite sensitive asthmatic children in primary care with house dust mite barrier bedding for six months failed to improve peak expiratory flow. Results strongly suggest that the intervention made no impact upon other clinical features of asthma.
doi:10.1186/1471-2296-3-12
PMCID: PMC116603  PMID: 12079502
7.  Asthma and other recurrent wheezing disorders in children (chronic) 
Clinical Evidence  2012;2012:0302.
Introduction
Childhood asthma is the most common chronic paediatric illness. There is no cure for asthma but good treatment to palliate symptoms is available. Asthma is more common in children with a personal or family history of atopy, increased severity and frequency of wheezing episodes, and presence of variable airway obstruction or bronchial hyperresponsiveness. Precipitating factors for symptoms and acute episodes include infection, house dust mites, allergens from pet animals, exposure to tobacco smoke, and exercise.
Methods and outcomes
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of single-agent prophylaxis in children taking as-needed inhaled beta2 agonists for asthma? What are the effects of additional prophylactic treatments in childhood asthma inadequately controlled by standard-dose inhaled corticosteroids? We searched: Medline, Embase, The Cochrane Library, and other important databases up to June 2010 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
Results
We found 48 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
Conclusions
In this systematic review we present information relating to the effectiveness and safety of the following interventions: beta2 agonists (long-acting), corticosteroids (inhaled standard or higher doses), leukotriene receptor antagonists (oral), omalizumab, and theophylline (oral).
Key Points
Childhood asthma can be difficult to distinguish from viral wheeze and can affect up to 20% of children.
Regular monotherapy with inhaled corticosteroids improves symptoms, reduces exacerbations, and improves physiological outcomes in children with asthma symptoms requiring regular short-acting beta2 agonist treatment. Their effect on final adult height is minimal and when prescribed within recommended doses have an excellent safety record. Regular monotherapy with other treatments is not superior to low-dose inhaled corticosteroids.
Leukotriene receptor antagonists may have a role as first-line prophylaxis in very young children.
There is consensus that long-acting beta2 agonists should not be used for first-line prophylaxis. CAUTION: Monotherapy with long-acting beta2 agonists does not reduce asthma exacerbations but may increase the chance of severe asthma episodes.
Theophylline was used as first-line prevention before the introduction of inhaled corticosteroids. Although there is weak evidence that theophylline is superior to placebo, theophylline should no longer be used as first-line prophylaxis in childhood asthma because of clear evidence of the efficacy and safety of inhaled corticosteroids. Theophylline has serious adverse effects (cardiac arrhythmia, convulsions) if therapeutic blood concentrations are exceeded.
When low-dose inhaled corticosteroids fail to control asthma, most older children will respond to one of the add-on options available, which include addition of long-acting beta2 agonists, addition of leukotriene receptor antagonists, addition of theophylline, or increased dose of inhaled corticosteroid. However, we don't know for certain how effective these additional treatments are because we found no/limited RCT evidence of benefit compared with adding placebo/no additional treatments. Addition of long-acting beta2 agonists may reduce symptoms and improve physiological measures compared with increased dose of corticosteroids in older children. Long-acting beta2 agonists are not currently licensed for use in children under 5 years of age.Consensus suggests that younger children are likely to benefit from addition of leukotriene receptor antagonists. Although there is weak evidence that addition of theophylline to inhaled corticosteroids does improve symptom control and reduce exacerbations, theophylline should only be added to inhaled corticosteroids in children aged over 5 years when the addition of long-acting beta2 agonists and leukotriene receptor antagonists have both been unsuccessful.
Omalizumab may be indicated in the secondary care setting for older children (aged over 5 years) with poorly controlled allergic asthma despite use of intermediate- and high-dose inhaled corticosteroids once the diagnosis is confirmed and compliance and psychological issues are addressed. However, we need more data to draw firm conclusions.
PMCID: PMC3285219  PMID: 22305975
8.  House dust mite sensitization in toddlers predict persistent wheeze in children between eight to fourteen years old 
Asia Pacific Allergy  2012;2(3):181-186.
Background
Identifying toddlers at increased risk of developing persistent wheeze provides an opportunity for risk-reducing interventions. House dust mite (HDM) allergen sensitization might identify this group of high-risk children.
Objective
We examined whether a positive skin prick test (SPT) to at least 1 of the 3 HDMs in wheezing toddlers, would serve as a predictor for persistent wheeze at age 8 to 14 years old.
Methods
A cohort of 78 children, who had wheezing episodes, and underwent SPT to 3 HDMs between the ages of 2 to 5 years old, were enrolled. SPT results were obtained from the National University Hospital database. Four to 9 years later, the children, currently between 8 to 14 years old, were re-assessed for persistence of asthma symptoms and other atopic disorders via a telephone interview. A validated questionnaire on current wheezing and asthma, developed by the International Study of Asthma and Allergies in Childhood, was used. Fisher's exact test was used to evaluate the association between persistence of asthma and a positive SPT.
Results
Of the 78 children who participated in the study, 42 (53.8%) had a positive SPT and 36 (46.2%) had a negative SPT. Of these, 18 (42.9%) of SPT positive and 7 (19.4%) of SPT negative children had persistence of asthma symptoms. There is a significant association between a positive SPT during the preschool years, and persistence of asthma (p = 0.0314 [<0.05]).
Conclusion
HDM sensitization at ages 2 to 5 years old in wheezing children predicts persistence of asthma after 4 to 9 years. This in turn may have benefits for management of asthma in this high-risk group.
doi:10.5415/apallergy.2012.2.3.181
PMCID: PMC3406297  PMID: 22872820
Dust mite; Allergy; Asthma; Wheezing; Skin tests; Child
9.  Effects of physical interventions on house dust mite allergen levels in carpet, bed, and upholstery dust in low-income, urban homes. 
Environmental Health Perspectives  2001;109(8):815-819.
House dust mite allergen exposure is a postulated risk factor for allergic sensitization, asthma development, and asthma morbidity; however, practical and effective methods to mitigate these allergens from low-income, urban home environments remain elusive. The purpose of this study was to assess the feasibility and effectiveness of physical interventions to mitigate house dust mite allergens in this setting. Homes with high levels of house dust mite allergen (Der f 1 + Der p 1 > or = 10 microg/g dust by enzyme-linked immunosorbent assay) in the bed, bedroom carpet, and/or upholstered furniture were enrolled in the study. Carpets and upholstered furniture were subjected to a single treatment of either dry steam cleaning plus vacuuming (carpet only) or intensive vacuuming alone. Bed interventions consisted of complete encasement of the mattress, box spring, and pillows plus either weekly professional or in-home laundering of nonencased bedding. Dust samples were collected at baseline and again at 3 days (carpet and upholstery only) and 2, 4, and 8 weeks posttreatment. We compared pretreatment mean allergen concentrations and loads to posttreatment values and performed between-group analyses after adjusting for differences in the pretreatment means. Both dry steam cleaning plus vacuuming and vacuuming alone resulted in a significant reduction in carpet house dust mite allergen concentration and load (p < 0.05). Levels approached pretreatment values by 4 weeks posttreatment in the intensive vacuuming group, whereas steam cleaning plus vacuuming effected a decrease that persisted for up to 8 weeks. Significant decreases in bed house dust mite allergen concentration and load were obtained in response to encasement and either professional or in-home laundering (p < 0.001). Between-group analysis revealed significantly less postintervention house dust mite allergen load in professionally laundered compared to home-laundered beds (p < 0.05). Intensive vacuuming and dry steam cleaning both caused a significant reduction in allergen concentration and load in upholstered furniture samples (p < 0.005). Based on these data, we conclude that physical interventions offer practical, effective means of reducing house dust mite allergen levels in low-income, urban home environments.
PMCID: PMC1240409  PMID: 11564617
10.  Effectiveness of education for control of house dust mites and cockroaches in Seoul, Korea 
We evaluated the efficacy of health education in reducing indoor arthropod allergens in Seoul. The mite control measures comprised the use of mite-proof mattress and pillow coverings, regular washing of potentially infested materials, maintenance of a low humidity, removal of carpets, and frequent vacuum cleaning. Cockroach control measures included trapping, application of insecticides, and protecting food. Of 201 homes enrolled in October 1999, 63 volunteers were included in a 2-year follow-up survey between April 2000 and January 2002. Before intervention, the density of mites/g of dust varied greatly; 27.1/g in children's bedding, 20/g in adult bedding, 7.2/g on the floors of children's bedrooms, 6.8/g in sofas, 5.9/g on the floors of adult's bedrooms, 3.9/g on living room floors, 3.7/g in carpets, and 1.9 mites/g on kitchen floors. The predominant mite species and house percentages infested were; Dermatophagoides farinae 93%, D. pteronyssinus 9%, and Tyrophagus putrescentiae 8%. Comparing 1999 and 2001 infestations, before and after 25 mo of education, mite abundance was reduced by 98%, from 23.7 to 0.57 mites/g of dust. In 1999, cockroaches were detected in 62% homes: 36% Blattella germanica and 35% Periplaneta spp., including 9% double infestations of B. germanica and P. americana. Following intervention, cockroach infestation rates decreased to 22% of houses in 2000 and 23% in 2001. We conclude that continuous and repetitive health education resulted in the effective control of domestic arthropods.
doi:10.3347/kjp.2006.44.1.73
PMCID: PMC2532652  PMID: 16514286
Blattella germanica; Dermatophagoides farinae; Periplaneta americana; Periplaneta fuliginosa; Periplaneta japonica; Tyrophagus putrescentiae; aeroallergens; allergy prevention; cockroaches; house dust mites
11.  House dust mite allergen avoidance and self-management in allergic patients with asthma: randomised controlled trial 
Background
The efficacy of bed covers that are impermeable to house dust mites has been disputed.
Aim
The aim of the present study was to investigate whether the combination of ‘house dust mite impermeable’ covers and a self-management plan, based on peak flow values and symptoms, leads to reduced use of inhaled corticosteroids (ICS) than self-management alone.
Design of study
Prospective, randomised, double blind, placebo-controlled trial.
Setting
Primary care in a south-eastern region of the Netherlands.
Method
Asthma patients aged between 16 and 60 years with a house dust mite allergy requiring ICS were randomised to intevention and placebo groups. They were trained to use a self-management plan based on peak flow and symptoms. After a 3-month training period, the intervention commenced using house dust mite impermeable and placebo bed covers. The follow-up period was 2 years. Primary outcome was the use of ICS; secondary outcomes were peak expiratory flow parameters, asthma control, and symptoms.
Results
One hundred and twenty-six patients started the intervention with house dust mite impermeable or placebo bed covers. After 1 and 2 years, significant differences in allergen exposure were found between the intervention and control groups (P<0.001). No significant difference between the intervention and control groups was found in the dose of ICS (P = 0.08), morning peak flow (P = 0.52), peak flow variability (P = 0.36), dyspnoea (P = 0.46), wheezing (P = 0.77), or coughing (P = 0.41). There was no difference in asthma control between the intervention and control groups.
Conclusion
House dust mite impermeable bed covers combined with self-management do not lead to reduced use of ICS compared with self-management alone.
PMCID: PMC2042544  PMID: 17359604
allergy; asthma; corticosteriods; house dust mites; inhalation; self management
12.  Mite and pet allergen levels in homes of children born to allergic and nonallergic parents: the PIAMA study. 
Environmental Health Perspectives  2002;110(11):A693-A698.
The Prevention and Incidence of Asthma and Mite Allergy (PIAMA) study is a birth cohort study that investigates the influence of allergen exposure on the development of allergy and asthma in the first several years of life. The objectives of this study were to investigate the relationship between a family history of allergy and/or asthma and exposure of newborn children to mite and pet allergen and to study the influence of different home and occupant characteristics on mite allergen exposure. Dust was sampled from the child's mattress and the parental mattress at 3 months after birth of the index child and analyzed for mite and pet allergens. Subjects were divided in groups according to history of asthma and allergy in their parents, and allergen exposure was studied in the different groups. Cat allergen exposure was significantly lower on parental mattresses in families with allergic mothers, but dog allergen exposure was not different. Mite allergen exposure was lower on parental mattresses in families with allergic mothers. Use of mite allergen-impermeable mattress covers reduced mite allergen exposure. Some other characteristics such as age of home and mattress were also found to influence mite allergen exposure. Parental mattresses in homes of allergic mothers had lower cat and mite (but not dog) allergen loadings than mattresses in homes of nonallergic parents. Paternal (as opposed to maternal) allergy seemed to have little influence.
PMCID: PMC1241089  PMID: 12417497
13.  Parental and neonatal risk factors for atopy, airway hyper-responsiveness, and asthma. 
Archives of Disease in Childhood  1996;75(5):392-398.
BACKGROUND: Previous studies have not resolved the importance of several potential risk factors for the development of childhood atopy, airway hyperresponsiveness, and wheezing, which would allow the rational selection of interventions to reduce morbidity from asthma. Risk factors for these disorders were examined in a birth cohort of 1037 New Zealand children. METHODS: Responses to questions on respiratory symptoms and measurements of lung function and airway responsiveness were obtained every two to three years throughout childhood and adolescence, with over 85% cohort retention at age 18 years. Atopy was determined by skin prick tests at age 13 years. Relations between parental and neonatal factors, the development of atopy, and features of asthma were determined by comparison of proportions and logistic regression. RESULTS: Male sex was a significant independent predictor for atopy, airway hyper-responsiveness, hay fever, and asthma. A positive family history, especially maternal, of asthma strongly predicted childhood atopy, airway hyperresponsiveness, asthma, and hay fever. Maternal smoking in the last trimester was correlated with the onset of childhood asthma by the age of 1 year. Birth in the winter season increased the risk of sensitisation to cats. Among those with a parental history of asthma or hay fever, birth in autumn and winter also increased the risk of sensitisation to house dust mites. The number of siblings, position in the family, socioeconomic status, and birth weight were not consistently predictive of any characteristic of asthma. CONCLUSIONS: Male sex, parental atopy, and maternal smoking during pregnancy are risk factors for asthma in young children. Children born in winter exhibit a greater prevalence of sensitisation to cats and house dust mites. These data suggest possible areas for intervention in children at risk because of parental atopy.
PMCID: PMC1511782  PMID: 8957951
14.  Effects of anti-mite measures on children with mite-sensitive asthma: a controlled trial. 
Thorax  1980;35(7):506-512.
Mite counts and tests for mite antigen were performed on samples of dust taken from the bedding of 53 children with mite-sensitive asthma. The samples from damp houses and the beds or enuretic children had markedly more mites and mite-antigen than those from dry houses. although the predominant species was usually Dermatophagoides pteronyssinus, some of the beds in the damp houses were heavily infested with another pyroglyphid mite Euroglyphus maynei, so that this was the species found in the greatest numbers. D pteronyssinus antigen was found to be correlated broadly with the total mite count, but more antigen was present for a given number of mites in the mattresses than in the blankets. The children were randomly allocated into two groups, one of which carried out rigorous anti-mite measures. The amounts of dust and mite antigen were reduced, though not the numbers of mites. Peak flow readings were monitored in the two groups for eight weeks and a final assessment made by a paediatrician who was unaware of the allocation of each patient in the trial. No significant differences emerged in the progress of the two groups, both tending to improve. Measures designed to remove mites from bedding do not greatly benefit the majority of children with mite-sensitive asthma.
PMCID: PMC471322  PMID: 7001667
15.  Indoor Environmental Exposures and Exacerbation of Asthma: An Update to the 2000 Review by the Institute of Medicine 
Background: Previous research has found relationships between specific indoor environmental exposures and exacerbation of asthma.
Objectives: In this review we provide an updated summary of knowledge from the scientific literature on indoor exposures and exacerbation of asthma.
Methods: Peer-reviewed articles published from 2000 to 2013 on indoor exposures and exacerbation of asthma were identified through PubMed, from reference lists, and from authors’ files. Articles that focused on modifiable indoor exposures in relation to frequency or severity of exacerbation of asthma were selected for review. Research findings were reviewed and summarized with consideration of the strength of the evidence.
Results: Sixty-nine eligible articles were included. Major changed conclusions include a causal relationship with exacerbation for indoor dampness or dampness-related agents (in children); associations with exacerbation for dampness or dampness-related agents (in adults), endotoxin, and environmental tobacco smoke (in preschool children); and limited or suggestive evidence for association with exacerbation for indoor culturable Penicillium or total fungi, nitrogen dioxide, rodents (nonoccupational), feather/down pillows (protective relative to synthetic bedding), and (regardless of specific sensitization) dust mite, cockroach, dog, and dampness-related agents.
Discussion: This review, incorporating evidence reported since 2000, increases the strength of evidence linking many indoor factors to the exacerbation of asthma. Conclusions should be considered provisional until all available evidence is examined more thoroughly.
Conclusion: Multiple indoor exposures, especially dampness-related agents, merit increased attention to prevent exacerbation of asthma, possibly even in nonsensitized individuals. Additional research to establish causality and evaluate interventions is needed for these and other indoor exposures.
Citation: Kanchongkittiphon W, Mendell MJ, Gaffin JM, Wang G, Phipatanakul W. 2015. Indoor environmental exposures and exacerbation of asthma: an update to the 2000 review by the Institute of Medicine. Environ Health Perspect 123:6–20; http://dx.doi.org/10.1289/ehp.1307922
doi:10.1289/ehp.1307922
PMCID: PMC4286274  PMID: 25303775
16.  Effect of dampness at home in childhood on bronchial hyperreactivity in adolescence 
Thorax  1998;53(12):1035-1040.
BACKGROUND—Relatively little is known about risk factors for the persistence of asthma and respiratory symptoms from childhood into adolescence, and few studies have included objective measurements to assess outcomes and exposure.
METHODS—From a large cross sectional study of all 4th grade school children in Munich (mean age 10.2 years), 234 children (5%) with active asthma were identified. Of these, 155 (66%) were reinvestigated with lung function measurements and bronchial provocation three years later (mean age 13.5years).
RESULTS—At follow up 35.5% still had active asthma. Risk factors for persisting asthma symptoms in adolescence were more severe asthma (OR 4.94; CI 1.65 to 14.76; p = 0.004) or allergic triggers (OR 3.54; CI 1.41 to 8.92; p = 0.007) in childhood. Dampness was associated with increased night time wheeze and shortness of breath but not with persisting asthma. Risk factors for bronchial hyperreactivity in adolescence were bronchial hyperreactivity in childhood (p= 0.004), symptoms triggered by allergen exposure (OR 5.47; CI 1.91 to 25.20; p = 0.029), and damp housing conditions (OR 16.14; CI 3.53 to 73.73; p<0.001). In a subgroup in whom house dust mite antigen levels in the bed were measured (70% of the sample), higher mite antigen levels were associated with bronchial hyperreactivity (OR per quartile of mite antigen 2.30; CI 1.03 to 5.12; p = 0.042). Mite antigen levels were also significantly correlated with dampness (p = 0.05). However, the effect of dampness on bronchial hyperreactivity remained significant when adjusting for mite allergen levels (OR 5.77; CI 1.17 to 28.44; p = 0.031).
CONCLUSION—Dampness at home is a significant risk factor for the persistence of bronchial hyperreactivity and respiratory symptoms in children with asthma. This risk is only partly explained by exposure to house dust mite antigen.


PMCID: PMC1745148  PMID: 10195075
17.  Indoor air pollution and childhood asthma: effective environmental interventions. 
Environmental Health Perspectives  1995;103(Suppl 6):55-58.
Exposure to indoor air pollutants such as tobacco smoke and dust mites may exacerbate childhood asthma. Environmental interventions to reduce exposures to these pollutants can help prevent exacerbations of the disease. Among the most important interventions is the elimination of environmental tobacco smoke from the environments of children with asthma. However, the effectiveness of reducing asthmatic children's exposure to environmental tobacco smoke on the severity of their symptoms has not yet been systematically evaluated. Dust mite reduction is another helpful environmental intervention. This can be achieved by enclosing the child's mattresses, blankets, and pillows in zippered polyurethane-coated casings. Primary prevention of asthma is not as well understood. It is anticipated that efforts to reduce smoking during pregnancy could reduce the incidence of asthma in children. European studies have suggested that reducing exposure to food and house dust mite antigens during lactation and for the first 12 months of life diminishes the development of allergic disorders in infants with high total IgE in the cord blood and a family history of atopy. Many children with asthma and their families are not receiving adequate counseling about environmental interventions from health care providers or other sources.
PMCID: PMC1518930  PMID: 8549490
18.  Factors associated with difference in prevalence of asthma in children from three cities in China: multicentre epidemiological survey  
BMJ : British Medical Journal  2004;329(7464):486.
Objective To determine the factors associated with difference in prevalence of asthma in children in different regions of China.
Design Multicentre epidemiological survey.
Setting Three cities in China.
Participants 10 902 schoolchildren aged 10 years.
Main outcome measures Asthma and atopic symptoms, atopic sensitisation, and early and current exposure to environmental factors.
Results Children from Hong Kong had a significantly higher prevalence of wheeze in the past year than those from Guangzhou and Beijing (odds ratio 1.64, 95% confidence interval 1.35 to 1.99). Factors during the first year of life and currently that were significantly associated with wheeze were cooking with gas (odds ratio 2.04, 1.34 to 3.13), foam pillows (2.58, 1.66 to 3.99), and damp housing (1.89, 1.26 to 2.83). Factors protecting against wheeze were cotton quilts and the consumption of fruit and raw vegetables.
Conclusion Environmental factors and diet may explain the differences in prevalence of asthma between children living in different regions of China.
PMCID: PMC515199  PMID: 15331473
19.  House dust mite control measures in the treatment of asthma 
Sensitization to the house dust mite (Dermataphagoides pteronyssinus) (HDM) is the most common risk factor associated with the development of asthma in adults and children. The effectiveness of HDM control measures in the treatment of asthma is not yet proven. The strategies for control for avoidance depend on our understanding of the biology of the HDM. The evidence suggests a favorable effect of transferring allergic asthmatic children to naturally low dust mite environments, such as at altitude or in hospital, but little to suggest that this can be replicated in general practice by simple practical measures such as mattress covers. However, a recent multi-allergen reduction approach has suggested benefits may be achievable. HDM densities tend to be high in warm, humid conditions in the home, which may be modified by external factors, such as ventilation. However, ventilation control to reduce indoor humidity has had inconsistent effects on dust mite levels and asthma. The challenge is to further refine the interventions in large placebo-controlled trials such that clinical outcomes may be more easily demonstrated.
PMCID: PMC1936356  PMID: 18360647
house dust mite; asthma; allergy; control
20.  Do Other Components of Bedding Dust Affect Sensitisation to House Dust Mites? 
ISRN Allergy  2012;2011:426941.
Bedding dust is a mixture of many components, of which the house dust mite (HDM) allergen, Der p 1, is the most allergenic. There has been little work to investigate the effect of other bedding dust components on HDM sensitisation. The objective of the study was to determine the effect of endotoxin in bedding dust on the allergic response in HDM-sensitised individuals. Twenty-nine house dust mite-sensitised adults were skin prick and allergen patch tested against a sterile solution of their own bedding dust and against a solution containing the same concentration of Der p 1 as the bedding solution for comparison. There was no significant difference in wheal size between the diluted house dust mite solution and the bedding dust in spite of their high levels of endotoxin. Symptomatic subjects had larger, but not statistically significant, responses to commercial house dust mite solution than asymptomatic subjects. Allergen patch test responses were negative in 22/29 of subjects using either bedding dust solutions or comparable diluted house dust mite solutions. An individual's own bedding dust does not appear to contain factors that enhance skin prick test or atopy patch test responses to house dust mites.
doi:10.5402/2011/426941
PMCID: PMC3658820  PMID: 23724237
21.  Encasing bedding in covers made of microfine fibers reduces exposure to house mite allergens and improves disease management in adult atopic asthmatics 
Background
Studies of avoidance of exposure to group 1 allergens of the Dermatophagoides group (Der p 1) have not yielded consistent improvements in adult asthma through avoidance. We explored whether the use of pillow and bed covers and allergen-avoidance counseling resulted in Der 1-level reduction, as measured by enzyme-linked immunosorbent assay, and thus improved asthma symptoms in adult patients.
Methods
Twenty-five adult patients with moderate or severe atopic asthma were randomized into intervention and control groups. Intervention patients slept on pillows and mattresses or futons encased in microfine-fiber covers and were counseled in allergen avoidance through bedroom cleaning. Control patients received neither special covers nor counseling. In the period August to October in 2009 (pre-intervention) and 2010 (post-intervention), dust samples were collected in open Petri dishes placed in bedrooms for 2 weeks and by rapid lifting of dust from bedding and skin using adhesive tape on the morning of 1 day of Petri dish placement. We examined the associations between changes in Der 1 level (as measured by enzyme-linked immunosorbent assay) and clinical symptom score, minimum % peak expiratory flow, and fraction of exhaled nitric oxide.
Results
Der 1 allergen levels on the mattress/futon covers and near the floor of the bedrooms of intervention patients, but not controls, were lower in 2010 than in 2009. From 2009 to 2010, asthma symptom scores decreased significantly, and minimum % peak expiratory flow increased significantly, in intervention patients. The fall in Der p 1 concentration was correlated with a reduction in the fraction of exhaled nitric oxide.
Conclusions
Minimization of Der 1 allergen exposure by encasing pillows and mattresses or futons and receiving counseling on avoiding exposure to indoor allergens improved asthma control in adult patients.
doi:10.1186/1710-1492-9-44
PMCID: PMC3829998  PMID: 24499343
Adult intervention; Allergen; Atopic asthma; Bed cover; Dermatophagoides; Group 1 mite antigen
22.  Potentially dangerous sleeping environments and accidental asphyxia in infancy and early childhood. 
Archives of Disease in Childhood  1994;71(6):497-500.
Infants and young children may be exposed to a variety of dangerous situations when left sleeping in cots, chairs, or beds. A review of 30 cases of accidental asphyxia occurring in infants and young children who had been left to sleep unattended was undertaken from the necropsy and consultation files of the Adelaide Children's Hospital. Causes of death included hanging from loose restrainers, clothing, or a curtain cord (12 cases), positional asphyxia/wedging from slipping between a mattress and bed/cot sides or wall, or from moving into a position where the face was covered and the upper airway occluded (16 cases), and suffocation from plastic bed covers (two cases). Cases of co-sleeping in bed with an adult and of non-accidental asphyxia were not included in this review. As the pathological findings were on occasion identical to those that are typically found in sudden infant death syndrome, adequate death scene examination was vital in several cases to allow identification of lethal sleeping environments and to enable steps to be taken to minimise the risk of future deaths due to similar situations. For example, two cases in which infants asphyxiated in rocking cradles led to the investigation of the cradles and to formulation of specific safety recommendations regarding the angle of tilt. Two infants who died after becoming wedged between the back of a couch and a co-sleeping parent in one case and cushions in the other, would indicate that this also represents a potentially lethal sleeping position. Other dangerous situations involved infant car seat restraints, seats with loose harnesses, cots with movable sides or projecting pieces, thin plastic mattress/pillow coverings, and beds with spaces between the mattress and cot side or wall. Lack of supervision at the time of death was a feature of each case.
Images
PMCID: PMC1030084  PMID: 7726607
23.  The Pattern of Sensitisation to Inhalant Allergens in Omani Patients with Asthma, Allergic Rhinitis and Rhinoconjunctivitis 
Objective:
Identification of relevant allergens that are prevalent in each environment which may have diagnostic and therapeutic implications in allergic diseases. This study aimed to identify the pattern of sensitisation to inhalant allergens in Omani patients with asthma, allergic rhinitis and rhinoconjunctivitis.
Methods:
The study was carried out during three consecutive years (2004–2006) at the allergy skin test laboratory of Sultan Qaboos University Hospital, Oman. Records of patients who had undergone an allergy skin prick test with a referring diagnosis of asthma, allergic rhinitis or rhinoconjunctivitis were reviewed. Two panels were used during the 3 years period. The frequencies of positive skin tests were analysed.
Results:
689 patients were tested, 384 for the first panel and 305 for the second panel. In the first panel, the commonest positive allergens were: house dust mites (37.8%), hay dust (35.4%), feathers (33.3%), sheep wool (26.6%), mixed threshing dust (25.8%), cat fur (24.2%), cockroach (22.7%), straw dust (22.7%), horse hair (17.4%), maize (16.1%), grasses (11.5%), cotton flock (10.7%), trees (10.4%), cow hair (7.8%), Alternaria alternata (3.6%), Aspergillus Niger (3.4%), and Aspergillus fumigatus (1.3%). In the second panel, the commonest positive allergens were also house dust mites: Dermatophagoides pteronyssinus (50.8%), Dermatophagoides farinae (47.9%); Mesquite (Prosopis glandulosa) (35.7%), Russian thistle (Salsola kali) (34.4%), cockroach (32.1%), Bermuda grass (Cynodon dactylon) (19.7%), grass mix-five standard (18.0%), wheat cultivate (14.1%), cats (13.8%), Penicillium notatum (4.3%), Alternaria tenius (3.9%), Aspergillus Niger (3.3%), feather mix (3.0%), dog (2.6%), horse hair and dander (2.6%), and Aspergillus fumigatus (1.6%).
Conclusion:
The pattern of sensitisation to environmental allergens in Oman seems to be similar to other reports from the Arabian Peninsula. Methods to identify and characterise environment specific allergens like a pollen survey may help in the management of patients with allergic asthma, allergic rhinitis and rhinoconjunctivitis.
PMCID: PMC3074841  PMID: 21748078
Asthma; Allergic; Rhinitis; Conjunctivitis; Allergens; Skin tests; Oman
24.  Weighted Road Density and Allergic Disease in Children at High Risk of Developing Asthma 
PLoS ONE  2014;9(6):e98978.
Background
Evidence for an association between traffic-related air pollution and allergic disease is inconsistent, possibly because the adverse effects may be limited to susceptible subgroups and these have not been identified. This study examined children in the Childhood Asthma Prevention Study (CAPS), potentially susceptible to air pollution effects because of a family history of asthma.
Methods
We examined cross-sectional associations at age eight years between road density within 75 m and 50 m of home address weighted by road type (traffic density), as a proxy for traffic-related air pollution, on the following allergic and respiratory outcomes: skin prick tests (SPTs), total and specific serum IgE, pre- and post-bronchodilator lung function, airway hyperresponsiveness, exhaled NO, and reported asthma and rhinitis.
Results
Weighted road density was positively associated with allergic sensitisation and allergic rhinitis. Adjusted relative risk (RR) for house dust mite (HDM) positive SPT was 1.25 (95% CI: 1.06–1.48), for detectable house dust mite-specific IgE was 1.19 (95% CI: 1.01–1.41) and for allergic rhinitis was 1.30 (95% CI: 1.03–1.63) per 100 m local road or 33.3 m motorway within 50 m of home. Associations were also seen with small decrements of peak and mid-expiratory flows and increased risk of asthma, current wheeze and rhinitis in atopic children.
Conclusion
Associations between road density and allergic disease were found in a potentially susceptible subgroup of children at high risk of developing atopy and asthma.
doi:10.1371/journal.pone.0098978
PMCID: PMC4064977  PMID: 24949625
25.  Characteristics and management of sublingual allergen immunotherapy in children with allergic rhinitis and asthma induced by house dust mite allergens 
Background
Allergen immunotherapy is a recognised intervention in patients with allergies not responding to standard pharmacotherapy or in whom pharmacotherapy is contraindicated. We describe the sublingual immunotherapy (SLIT) regimens used in children and adolescents with house dust mite (HDM) respiratory allergies in France and assess the efficacy and safety of this treatment.
Methods
This was a sub-analysis of paediatric patients included in a previous retrospective, observational, multicentre study. Inclusion criteria were: age 5–17 years; respiratory allergy and proven sensitisation to HDM; at least 2 years follow-up after SLIT initiation. The following data were recorded at SLIT initiation: clinical characteristics; sensitisation profile; concomitant symptomatic medications; details of SLIT protocol. During follow-up and at the end of treatment the following data were recorded: any changes to SLIT treatment; any changes to symptomatic medications; symptom progression; adverse events. SLIT efficacy, patient compliance and satisfaction, and safety were assessed.
Results
736 paediatric patients were included in this analysis. Most patients (95.5%) had allergic rhinitis, which was moderate to severe persistent in 62.8%. Allergic asthma was present in 64.0% and was mild to moderate persistent in 52.7% of these patients. The majority of patients had rhinitis with asthma (59.5%). Three-hundred and seventy five (62.3%) patients were polysensitised. Compliance was good in 86.5% of patients and SLIT was effective in 83.8%. Symptoms of rhinitis and asthma were improved in 64.6% and 64.3% of patients, respectively. A decrease in symptomatic medication was observed following SLIT initiation in patients with rhinitis and/or asthma. SLIT was well tolerated with mainly local reactions reported.
Conclusions
HDM SLIT appears to be effective in children and adolescents with rhinitis and/or asthma due to HDM allergens, with no tolerability issues and similar benefits as in adults.
doi:10.1186/2045-7022-4-15
PMCID: PMC4047545  PMID: 24910771
Adolescents; Allergy; Asthma; Children; House dust mite; Rhinitis; Sublingual immunotherapy

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