Asthma Management Handbook

Asthma prevention in children at risk of developing asthma

Recommendations

Advise parents/carers to ensure babies and children are not exposed to cigarette smoke.

How this recommendation was developed

Adapted from existing guidance

Based on reliable clinical practice guideline(s) or position statement(s):

  • ASCIA 20091
  • RACGP 20142

Last reviewed version 2.0

If a family already has pets, it is not necessary to remove them to reduce a child’s risk of developing asthma, unless the child develops clinical evidence of pet allergy and this is confirmed by skin-prick or allergen-specific IgE testing.

How this recommendation was developed

Adapted from existing guidance

Based on reliable clinical practice guideline(s) or position statement(s):

  • ASCIA3

Last reviewed version 2.0

 

In children without demonstrated specific hypersensitivities, do not routinely recommend allergen avoidance measures for the purpose of reducing the child’s risk of developing asthma.

How this recommendation was developed

Consensus

Based on clinical experience and expert opinion (informed by evidence, where available).

Last reviewed version 2.0

Do not recommend single allergen avoidance measures (e.g. house dust mite-impermeable mattress covers) for the purpose of reducing the child’s risk of developing asthma.

How this recommendation was developed

Evidence-based recommendation

Based on literature search and formulated by multidisciplinary working group

Key evidence considered:

  • Arroyave et al. 20144
  • Maas et al. 20095
  • Gehring et al. 20126

Last reviewed version 2.0

Advise parents/carers that damp, mouldy home environments may increase asthma risk in children and should be avoided if possible (e.g. by ventilation and mould removal), but that there is not clear evidence that anti-mould strategies will prevent asthma.

Note: Exposure to potentially harmful fumes from chemicals in cleaning products (e.g. chlorine bleach) should also be avoided.

How this recommendation was developed

Consensus

Based on clinical experience and expert opinion (informed by evidence, where available), with particular reference to the following source(s):

  • Quansah et al. 20127
  • Tischer et al. 20118
  • Dotterud et al. 20139

Last reviewed version 2.0

Advise parents/carers that children’s risk of developing asthma may be increased by various types of indoor and outdoor pollution (e.g. unflued gas heaters, traffic pollution).

How this recommendation was developed

Evidence-based recommendation

Based on literature search and formulated by multidisciplinary working group.

Key evidence considered:

  • Khreis et al. 201710
  • Quansah et al 20127
  • Gasana et al. 201211
  • Tischer et al. 20118
  • Patelarou et al. 201512
  • Jaakkola & Knight. 200813
  • Ponsonby et al. 200014

Last reviewed version 2.0

Advise parents/carers to avoid unnecessary paracetamol use, but to give children paracetamol at recommended doses when indicated and according to current guidelines for managing fever or pain.

How this recommendation was developed

Consensus

Based on clinical experience and expert opinion after literature review yielded insufficient evidence for an evidence-based recommendation

Key evidence considered:

  • Cheelo et al. 201515
  • Heintze et al. 201316
  • Etminan et al. 200917
  • Wickens et al. 201118
  • Bakkeheim et al. 201119
  • Amberbi, et al. 201120
  • Kreiner-Møller et al. 201221
  • Lowe et al. 201022
  • Kurukulaaratchy et al. 201223
  • Koniman et al. 200724
  • Rusconi et al. 201125
  • Kuschnir et al. 200726
  • Vlaski, et al. 200727
  • Foliaki et al. 200828
  • Garcia et al. 200829
  • Del-Rio-Navarro et al. 200830
  • Del-Rio-Navarro et al. 200631
  • Beasley et al. 201132
  • Beasley et al. 200833
  • Karimi et al. 200634
  • Barragán Meijueiro et al. 200635
  • Sharma & Banga 200736
  • Wong et al. 200737
  • Cohet et al. 200438
  • Rodriguez-Martinez et al. 200839

Last reviewed version 2.0

Prescribe antibiotics, proton pump inhibitors or antacids for children as indicated and where a clinical benefit is likely, but avoid unnecessary use.
 

How this recommendation was developed

Consensus recommendation following inconclusive literature search

Based on clinical experience and expert opinion after literature review yielded insufficient evidence for an evidence-based recommendation

Key evidence considered:

  • Heintze et al. 201316
  • Mitre et al. 201840

Last reviewed version 2.0

In children with atopic dermatitis or allergic rhinitis, manage according to current guidelines (including with antihistamines, if indicated) but do not prescribe or recommend long-term antihistamine treatment specifically for the purpose of reducing the child’s risk of developing asthma.

How this recommendation was developed

Consensus recommendation following inconclusive literature search

Based on clinical experience and expert opinion after literature review yielded insufficient evidence for an evidence-based recommendation

Key evidence considered:

  • Early Treatment of the Atopic Child Study Group. 199841

Last reviewed version 2.0

Consider specific allergen immunotherapy in children with allergic rhinitis who have a history of proven, clinically important sensitisation to a particular allergen that cannot feasibly be avoided and for which for specific allergen immunotherapy is available.

Note: Specific allergen immunotherapy is indicated for the management of allergy, not prevention of asthma. However, early treatment before the onset of asthma may reduce the risk of asthma symptoms and asthma medication requirements.

Note: Make sure parents understand that treatment must be long term (3–5 years), and understand the cost and risks of the treatment.

Note: TGA-approved indications for commercially available preparations vary according to age group.

How this recommendation was developed

Consensus

Based on clinical experience and expert opinion (informed by evidence, where available), with particular reference to the following source(s):

  • Kristiansen et al. 201742
  • Valovirta et al. 201843
  • Jacobsen et al. 200744
  • Novembre et al. 200445

Last reviewed version 2.0

 

More information

Smoking: effects on risk of developing asthma

Exposure to tobacco smoke toxins in utero or in infancy has been associated with increased risk of wheezing and asthma in children.46, 47

Maternal smoking during pregnancy is associated with an almost twofold increase in asthma in infants aged 2 years or less.47

Several large systematic reviews and meta-analyses of prospective cohort studies have reported that maternal smoking during pregnancy and exposure to tobacco smoke in infancy are associated with large increases in the risk of wheezing in the first 2 years of life.47, 48

A meta-analysis of observational studies (mainly cross-sectional studies) found that exposure to environmental tobacco smoke was associated with an increase in childhood asthma,49 but this association was weaker than that between exposure to environmental tobacco smoke and wheezing.

Epigenetic effects may modify the effects of environmental risk factors, including exposure to tobacco smoke, on development of asthma.50 However, a longitudinal cohort study51 found no association between smoking by grandparents (including during pregnancy with the mothers of the study cohort) early wheezing or asthma at age 7 in grandchildren.

Last reviewed version 2.0

Close
Pets: effects on risk of developing asthma

Some studies have identified perinatal exposure to pets (dogs or cats) as a potentially protective factor against allergic disease, but results are inconsistent between studies.52

This effect appears to genotype dependent. A recent large prospective study found that exposure to pets (especially cats) from birth reduced the risk of childhood asthma, pneumonia, and bronchiolitis in genetically susceptible children.53

Last reviewed version 2.0

Close
Allergies and exposure to allergens: effects on risk of developing asthma

Note: Although allergic asthma is common, non-allergic asthma also occurs.

Population-based studies have observed a positive association between early life exposure to aeroallergens (house dust mite, mould)54 or sensitisation to aeroallergens55 and the development of asthma. However, exposure to allergens may not actually cause asthma.55

Allergic rhinitis is a major risk factor for asthma and often precedes it.56, 57, 58 These associations probably reflect the common allergic causes of both conditions, rather than a causal link.58

The combination of sensitisation to aeroallergens and viral infections early in life increases asthma risk.59

Last reviewed version 2.0

Close
Allergen avoidance in children: effects on risk of developing asthma

There is accumulating evidence from systematic reviews of intervention trials that single allergen reduction strategies, such as the use of mattress covers that are impermeable to house dust mite, are not effective in preventing the development of wheezing or asthma in children.4, 5

An Australian controlled clinical trial that compared house dust mite avoidance (acaricide and impermeable mattress covers), from birth to 5 years, with simple advice on cleaning, vacuuming, dusting and maintaining adequate ventilation,60, 61 reported no reduction in the risk of developing asthma at age 11.5 years.62

Multimodal allergen avoidance strategies that reduce exposure to both inhalant and food allergens, beginning in late pregnancy or from birth, may reduce the risk of asthma in children under 5 and in children over 5 years.5 However, these strategies require intensive effort and may not be feasible for many families.

Avoiding exposure to pets does not reduce asthma risk.63 There is even limited evidence that perinatal exposure to dogs or cats could reduce the risk of allergic disease.52

Last reviewed version 2.0

Close
Traffic air pollution: effects on risk of developing asthma

There is mounting evidence from observational studies for an association between pollution and asthma risk in children. However, it is difficult to control for the influence of confounding factors such as socioeconomic status.

In systematic reviews and meta-analyses:

  • prenatal exposure to air pollution (including nitrogen dioxide, particulate matter) was associated with increased risk of wheezing and asthma in children64
  • early life exposure to air pollution (nitrogen dioxide, ozone, volatile organic compounds, and particulate matter) was associated with increased risk of allergic asthma in children54
  • childhood exposure to traffic pollution including black carbon (soot from vehicle emissions), nitrogen dioxide, fine particulate matter, carbon monoxide and particulate matter, were associated with increased risk of asthma.10, 11

The role of traffic-related air pollution in the development of adult-onset asthma is less conclusive than in childhood asthma due to fewer studies and heterogeneity among studies.65

Last reviewed version 2.0

Close
Indoor air pollution: effects on risk of developing asthma

Epidemiological studies have consistently reported an association between early life exposure to indoor dampness and mould (particularly visible mould and mould odour)7 and increased risk of developing asthma or wheeze.766678 However, it is difficult to control for the influence of confounding factors such as socioeconomic status.

Exposure to fumes from polyvinyl chloride products (PVC) surface materials is associated with increased risk of asthma in children, while exposure to heated PVC fumes (mainly in the workplace) is associated with increased risk of asthma in adults.13

The use of gas stoves or ovens in the home has also been associated with development of asthma in children.68

Various indoor pollutants have also been associated with increased risk of adult-onset asthma. These include airborne substances used in the home (e.g. cleaning sprays)69 and many airborne substances encountered in workplaces.

Last reviewed version 2.0

Close
Paracetamol: effects on risk of developing asthma

Prenatal and childhood paracetamol use has been associated with increased asthma risk in several observational studies. However, causality has not been demonstrated. The effect is small, and the association may be due to confounding by indication.

Health professionals can advise pregnant women that there is some evidence from around the world that paracetamol use in pregnancy might increase the baby’s risk of wheezing or asthma, but that paracetamol is still considered the best option for pain relief in pregnant women.70

Prenatal exposure

Meta-analyses of observational studies (mainly prospective cohorts) show that paracetamol use during pregnancy is associated with increases in the risk of wheeze in early childhood and of childhood asthma at age 5 or older.46, 15, 71, 72, 17 However, this finding must be interpreted with caution because of heterogeneity among studies and the fact that some studies did not control for maternal respiratory tract infections.

Early life exposure

Several systematic reviews have reported an association between paracetamol use in infancy and development of asthma.16, 71, 17 However, many of the included studies were of low quality and the association may be due to confounding.

A meta-analysis of observational studies found that increasing frequency of use of paracetamol during infancy was associated with a small increase in the risk of childhood asthma, but the effect was reduced to very small after adjusting for respiratory tract infections.15 A recent systematic review of systematic reviews (overview)46 concluded that there was no significant association between paracetamol use during infancy and childhood asthma, after adjustment for lower respiratory tract infections.

Last reviewed version 2.0

Close
Proton pump inhibitors and H2 receptor antagonists

Associations between acid-suppressive medicines and allergic disease have been reported in observational studies.

The use of acid-suppressive medication during pregnancy has been associated with increased risk of asthma and allergy in the offspring.73, 74, 75, 76

A retrospective study of a large cohort of US children reported that children prescribed H2 receptor antagonists or proton pump inhibitors during the first 6 months of infancy had a significant increases in the risk of subsequent asthma.40

Last reviewed version 2.0

Close
Antihistamines in children with allergies: effects on risk of developing asthma

Long-term antihistamine treatment has been investigated as a strategy for preventing the development of asthma in children with allergies.

In a single multi-country, double-blind, randomised, placebo-controlled trial in children aged 1–2 years with atopic dermatitis,77 18 months’ treatment with cetirizine (0.25mg/kg twice daily) did not reduce the risk of developing asthma, compared with placebo. However, in the subgroup of children sensitised to grass pollen or house dust mite, cetirizine treatment was associated with a reduction in the rate of new asthma diagnoses, compared with placebo.77

Last reviewed version 2.0

Close
Specific allergen immunotherapy (desensitisation): effects on risk of developing asthma

Note: Specific allergen immunotherapy is prescribed for allergic rhinitis, not for asthma prevention.

Few randomised controlled trials have been designed to evaluate specific allergen immunotherapy in children with allergic rhinitis who do not have asthma. Each of the available studies has reported a reduction in the onset of asthma.

A systematic review found that specific allergen immunotherapy in children with allergic rhinitis was associated with a short-term reduction in the risk developing asthma.42 However, this benefit was not maintained long term. Overall, immunotherapy did not reduce the risk of developing a first allergic disease over the short term.42

A recent randomised controlled trial evaluated 3 years’ treatment with SQ grass sublingual immunotherapy in children aged 5–12 years with a clinically relevant history of grass pollen allergic rhinoconjunctivitis and no medical history or signs of asthma at baseline. At follow-up 2 years after finishing treatment, immunotherapy did not affect time to onset of asthma diagnosis (defined by reversible airflow limitation).78 However, immunotherapy reduced the risk of experiencing asthma symptoms or using asthma medication at the end of 3 years’ treatment, during the 2-year posttreatment follow-up, and during the entire 5-year trial period.78

Last reviewed version 2.0

Close
Maternal and childhood obesity: effects on risk of developing asthma

Maternal obesity during pregnancy increases the risk of asthma or wheeze in children, based on a meta-analysis of observational studies.79

High gestational weight gain was also associated with higher risk of asthma or wheeze.79

Childhood overweight or obesity have also been associated with increased risk of developing asthma in some systematic reviews of observational studies.80, 81, 82

Last reviewed version 2.0

Close
Aetiology of exercise-induced bronchoconstriction

Both genetics and environment may contribute to exercise-induced bronchoconstriction.83

Exercise-induced bronchoconstriction occurs when a person’s ventilatory rate is high and their airways must heat and humidify a large volume of air in a short time. Dehydration of the airway leads to release of inflammatory mediators within the airway and contraction of airway smooth muscle.83 Dry air is one risk factor.83

Exercise-induced bronchoconstriction in athletes who do not have chronic asthma may have different pathogenesis and presentation than exercise-induced bronchoconstriction in people with asthma.83 Elite athletes often report onset of exercise-induced bronchoconstriction after age 20 years and after many years of high-level training.84

In elite athletes, exercise-induced bronchoconstriction is probably due to chronic injury to airway epithelium associated with long-term frequent prolonged high ventilation rates in the presence of environmental exposure to cold air, dry air, and airborne pollutants such as ozone, particulate matter:

  • The high prevalence of exercise-induced bronchoconstriction in ice-rink athletes has been linked to inhalation of cold dry air in combination with airborne pollutants from fossil-fuelled ice resurfacing machines
  • Exercise-induced bronchoconstriction in skiers and other winter athletes has been linked to injury of airway epithelium due to conditioning large volumes of cold dry air858687
  • The high prevalence of asthma and exercise-induced bronchoconstriction reported among competitive swimmers has been associated with exposure to chlorine in indoor swimming pools8588, 89
  • The increased prevalence of exercise-induced bronchoconstriction among distance runners, compared with the general population, has been attributed to exposure to high levels of airborne allergens and ozone8385
  • Certain airborne viruses inhaled during exercise may also contribute to exercise-induced bronchoconstriction.83
Close

References

  1. Australasian Society of Clinical Immunology and Allergy,. Allergy prevention in children. ASCIA, 2009.
  2. Royal Australian College of General Practitioners,. Supporting smoking cessation. A guide for health professionals. RACGP, 2014. Available from: https://www.racgp.org.au/your-practice/guidelines/smoking-cessation/
  3. Australasian Society of Clinical Immunology and Allergy,. Allergy prevention frequently asked questions. ASCIA, 2016.
  4. Arroyave, W. D., Rabito, F. A., Carlson, J. C., et al. Impermeable dust mite covers in the primary and tertiary prevention of allergic disease: a meta-analysis. Ann Allergy Asthma Immunol. 2014; 112: 237-48. Available from: https://www.ncbi.nlm.nih.gov/pubmed/24484971
  5. Maas, T, Kaper, J, Sheikh, A, et al. Mono and multifaceted inhalant and/or food allergen reduction interventions for preventing asthma in children at high risk of developing asthma. Cochrane Database Syst Rev. 2009; Issue 3: . Available from: http://cochranelibrary-wiley.com/doi/10.1002/14651858.CD006480.pub2/abstract
  6. Gehring, U., de Jongste, J. C., Kerkhof, M., et al. The 8-year follow-up of the PIAMA intervention study assessing the effect of mite-impermeable mattress covers. Allergy. 2012; 67: 248-56. Available from: https://www.ncbi.nlm.nih.gov/pubmed/22023655
  7. Quansah, R., Jaakkola, M. S., Hugg, T. T., et al. Residential dampness and molds and the risk of developing asthma: a systematic review and meta-analysis. PLoS One. 2012; 7: e47526. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23144822
  8. Tischer, C. G., Hohmann, C., Thiering, E., et al. Meta-analysis of mould and dampness exposure on asthma and allergy in eight European birth cohorts: an ENRIECO initiative. Allergy. 2011; 66: 1570-9. Available from: https://www.ncbi.nlm.nih.gov/pubmed/21923669
  9. Dotterud, C. K., Storro, O., Simpson, M. R., et al. The impact of pre- and postnatal exposures on allergy related diseases in childhood: a controlled multicentre intervention study in primary health care. BMC Public Health. 2013; 13: 123. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23394141
  10. Khreis, H., Kelly, C., Tate, J., et al. Exposure to traffic-related air pollution and risk of development of childhood asthma: A systematic review and meta-analysis. Environ Int. 2017; 100: 1-31. Available from: https://www.ncbi.nlm.nih.gov/pubmed/27881237
  11. Gasana, J, Dillikar, D, Mendy, A, et al. Motor vehicle air pollution and asthma in children: a meta-analysis. Environ Res. 2012; 117: 36-45. Available from: https://www.ncbi.nlm.nih.gov/pubmed/22683007
  12. Patelarou, E., Tzanakis, N., Kelly, F. J.. Exposure to indoor pollutants and Wheeze and asthma development during early childhood. Int J Environ Res Public Health. 2015; 12: 3993-4017. Available from: https://www.ncbi.nlm.nih.gov/pubmed/25872014
  13. Jaakkola, J. J., Knight, T. L.. The role of exposure to phthalates from polyvinyl chloride products in the development of asthma and allergies: a systematic review and meta-analysis. Environ Health Perspect. 2008; 116: 845-53. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2453150/
  14. Ponsonby, A. L., Couper, D., Dwyer, T., et al. The relation between infant indoor environment and subsequent asthma. Epidemiology. 2000; 11: 128-35. Available from: https://www.ncbi.nlm.nih.gov/pubmed/11021608
  15. Cheelo, M., Lodge, C. J., Dharmage, S. C., et al. Paracetamol exposure in pregnancy and early childhood and development of childhood asthma: a systematic review and meta-analysis. Arch Dis Child. 2015; 100: 81-9. Available from: https://www.ncbi.nlm.nih.gov/pubmed/25429049
  16. Heintze, K., Petersen, K. U.. The case of drug causation of childhood asthma: antibiotics and paracetamol. Eur J Clin Pharmacol. 2013; 69: 1197-209.
  17. Etminan, M, Sadatsafavi, M, Jafari, S, et al. Acetaminophen use and the risk of asthma in children and adults: a systematic review and metaanalysis. Chest. 2009; 136: 1316-1323.
  18. Wickens, K, Beasley, R, Town, I, et al. The effects of early and late paracetamol exposure on asthma and atopy: a birth cohort. Clin Exp Allergy. 2011; 41: 399-406.
  19. Bakkeheim, E, Mowinckel, P, Carlsen, K H, et al. Paracetamol in early infancy: the risk of childhood allergy and asthma. Acta Paediatr. 2011; 100: 90-96.
  20. Amberbir, A, Medhin, G, Alem, A, et al. The role of acetaminophen and geohelminth infection on the incidence of wheeze and eczema: a longitudinal birth-cohort study. Am J Respir Crit Care Med. 2011; 183: 165-179.
  21. Kreiner-Møller, E, Sevelsted, A, Vissing, N H, et al. Infant acetaminophen use associates with early asthmatic symptoms independently of respiratory tract infections: the Copenhagen Prospective Study on Asthma in Childhood 2000 (COPSAC(2000)) cohort. J Allergy Clin Immunol. 2012; 130: 1434-1436.
  22. Lowe, A J, Carlin, J B, Bennett, C M, et al. Paracetamol use in early life and asthma: prospective birth cohort study. BMJ. 2010; 341: c4616.
  23. Kurukulaaratchy, R J, Raza, A, Scott, M, et al. Characterisation of asthma that develops during adolescence; findings from the Isle of Wight Birth Cohort. Respir Med. 2012; 106: 329-327.
  24. Koniman, R, Chan, Y H, Tan, T N, Van Bever, H P. A matched patient-sibling study on the usage of paracetamol and the subsequent development of allergy and asthma. Pediatr Allergy Immunol. 2007; 18: 128-134.
  25. Rusconi, F, Gagliardi, L, Galassi, C, et al. Paracetamol and antibiotics in childhood and subsequent development of wheezing/asthma: association or causation?. Int J Epidemiol. 2011; 40: 662-667.
  26. Kuschnir, F C, Alves da Cunha, A J. Environmental and socio-demographic factors associated to asthma in adolescents in Rio de Janeiro, Brazil. Pediatr Allergy Immunol. 2007; 18: 142-148.
  27. Vlaski, E, Stavric, K, Isjanovska, R, et al. Acetaminophen intake and risk of asthma, hay fever and eczema in early adolescence. Iran J Allergy Asthma Immunol. 2007; 6: 143-149.
  28. Foliaki, S, Annesi-Maesano, I, Tuuau-Potoi, N, et al. Risk factors for symptoms of childhood asthma, allergic rhinoconjunctivitis and eczema in the Pacific: an ISAAC Phase III study. Int J Tuberc Lung Dis. 2008; 12: 799-806.
  29. Garcia, E, Aristizabal, G, Vasquez, C, et al. Prevalence of and factors associated with current asthma symptoms in school children aged 6-7 and 13-14 yr old in Bogotá, Colombia. Pediatr Allergy Immunol. 2008; 19: 307-314.
  30. Del-Rio-Navarro, B E, Ito-Tsuchiya, F M, Berber, A, et al. Study of the relationship between acetaminophen and asthma in Mexican children aged 6 to 7 years in 3 Mexican cities using ISAAC methodology. J Investig Allergol Clin Immunol. 2008; 18: 194-201.
  31. Del-Rio-Navarro, B, Berber, A, Blandón-Vijil, V, et al. Identification of asthma risk factors in Mexico City in an International Study of Asthma and Allergy in Childhood survey. Allergy Asthma Proc. 2006; 27: 325-333.
  32. Beasley, R W, Clayton, T O, Crane, J, et al. Acetaminophen use and risk of asthma, rhinoconjunctivitis, and eczema in adolescents: International Study of Asthma and Allergies in Childhood Phase Three. Am J Respir Crit Care Med. 2011; 183: 171-178.
  33. Beasley, R, Clayton, T, Crane, J, et al. Association between paracetamol use in infancy and childhood, and risk of asthma, rhinoconjunctivitis, and eczema in children aged 6?7 years: analysis from Phase Three of the ISAAC programme. Lancet. 2008; 372: 1039-1048. Available from: http://linkinghub.elsevier.com/retrieve/pii/S0140673608614452
  34. Karimi, M, Mirzaei, M, Ahmadieh, M H. Acetaminophen use and the symptoms of asthma, allergic rhinitis and eczema in children. Iran J Allergy Asthma Immunol. 2006; 5: 63-67.
  35. Barragán-Meijueiro, M M, Morfín-Maciel, B, Nava-Ocampo, A A. Mexican population-based study on exposure to acetaminophen and the risk of wheezing, rhinitis, and eczema in childhood. J Investig Allergol Clin Immunol. 2006; 16: 247-252.
  36. Sharma, S K, Banga, A. Prevalence and risk factors for wheezing in children from rural areas of north India. Allergy Asthma Proc. 2007; 28: 647-653.
  37. Wong, G W, Leung, T F, May, Y, et al. Symptoms of asthma and atopic disorders in preschool children: prevalence and risk factors. Clin Exp Allergy. 2007; 37: 174-179.
  38. Cohet, C, Cheng, S, MacDonald, C, et al. Infections, medication use, and the prevalence of symptoms of asthma, rhinitis, and eczema in childhood. J Epidemiol Community Health. 2004; : .
  39. Rodriguez Martinez, C, Sossa, M, Goss, C H. Factors associated with severe disease in a population of asthmatic children of Bogota, Colombia. J Asthma. 2008; 45: 141-147.
  40. Mitre, E., Susi, A., Kropp, L. E., et al. Association between use of acid-suppressive medications and antibiotics during infancy and allergic diseases in early childhood. JAMA Pediatr. 2018; 172: e180315. Available from: https://www.ncbi.nlm.nih.gov/pubmed/29610864
  41. Early Treatment of the Atopic Child Study Group,. Allergic factors associated with the development of asthma and the influence of cetirizine in a double-blind, randomised, placebo-controlled trial: first results of ETAC. Early Treatment of the Atopic Child. Pediatr Allergy Immunol. 1998; 9: 116-124.
  42. Kristiansen, M., Dhami, S., Netuveli, G., et al. Allergen immunotherapy for the prevention of allergy: A systematic review and meta-analysis. Pediatr Allergy Immunol. 2017; 28: 18-29. Available from: https://www.ncbi.nlm.nih.gov/pubmed/27653623
  43. Valovirta, E., Boza, M. L., Robertson, C. F., et al. Intermittent or daily montelukast versus placebo for episodic asthma in children. Ann Allergy Asthma Immunol. 2011; 106: 518-26. Available from: https://www.ncbi.nlm.nih.gov/pubmed/21624752
  44. Jacobsen, L., Niggemann, B., Dreborg, S., et al. Specific immunotherapy has long-term preventive effect of seasonal and perennial asthma: 10-year follow-up on the PAT study. Allergy. 2007; 62: 943-8. Available from: https://www.ncbi.nlm.nih.gov/pubmed/17620073
  45. Novembre, E, Galli, E, Landi, F, et al. Coseasonal sublingual immunotherapy reduces the development of asthma in children with allergic rhinoconjunctivitis. J Allergy Clin Immunol. 2004; 114: 851-857. Available from: https://www.ncbi.nlm.nih.gov/pubmed/15480326
  46. Castro-Rodriguez, J. A., Forno, E., Rodriguez-Martinez, C. E., Celedon, J. C.. Risk and protective factors for childhood asthma: what is the evidence?. J Allergy Clin Immunol Pract. 2016; 4: 1111-1122. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5107168/
  47. Burke, H., Leonardi-Bee, J., Hashim, A., et al. Prenatal and passive smoke exposure and incidence of asthma and wheeze: systematic review and meta-analysis. Pediatrics. 2012; 129: 735-44. Available from: https://www.ncbi.nlm.nih.gov/pubmed/22430451/
  48. Vardavas, C. I., Hohmann, C., Patelarou, E., et al. The independent role of prenatal and postnatal exposure to active and passive smoking on the development of early wheeze in children. Eur Respir J. 2016; 48: 115-24. Available from: http://erj.ersjournals.com/content/48/1/115.long
  49. Tinuoye, O., Pell, J. P., Mackay, D. F.. Meta-analysis of the association between secondhand smoke exposure and physician-diagnosed childhood asthma. Nicotine Tob Res. 2013; 15: 1475-83. Available from: https://www.ncbi.nlm.nih.gov/pubmed/23539174
  50. Harb, H., Alashkar Alhamwe, B., Garn, H., et al. Recent developments in epigenetics of pediatric asthma. Curr Opin Pediatr. 2016; 28: 754-763. Available from: https://www.ncbi.nlm.nih.gov/pubmed/27662207
  51. Miller, L. L., Henderson, J., Northstone, K., et al. Do grandmaternal smoking patterns influence the etiology of childhood asthma?. Chest. 2014; 145: 1213-1218. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24158349
  52. Lodge, C. J., Allen, K. J., Lowe, A. J., et al. Perinatal cat and dog exposure and the risk of asthma and allergy in the urban environment: a systematic review of longitudinal studies. Clin Dev Immunol. 2012; 2012: 176484. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22235226
  53. Stokholm, J., Chawes, B. L., Vissing, N., et al. Cat exposure in early life decreases asthma risk from the 17q21 high-risk variant. J Allergy Clin Immunol. 2018; 141: 1598-1606. Available from: https://www.ncbi.nlm.nih.gov/pubmed/29102067
  54. Gaffin, J. M., Kanchongkittiphon, W., Phipatanakul, W.. Perinatal and early childhood environmental factors influencing allergic asthma immunopathogenesis. Int Immunopharmacol. 2014; 22: 21-30. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4119505/
  55. Arshad, S H. Does exposure to indoor allergens contribute to the development of asthma and allergy?. Curr Allergy Asthma Rep. 2010; 10: 49-55.
  56. Pawankar, R, Bunnag, C, Chen, Y, et al. Allergic rhinitis and its impact on asthma update (ARIA 2008)–western and Asian-Pacific perspective. Asian Pac J Allergy Immunol. 2009; 27: 237-243. Available from: http://apjai-journal.org/wp-content/uploads/2017/12/9AllergicRhinitisandItsImpactVol-27No4December2009P.pdf
  57. Burgess, J A, Walters, E H, Byrnes, G B, et al. Childhood allergic rhinitis predicts asthma incidence and persistence to middle age: a longitudinal study. J Allergy Clin Immunol. 2007; 120: 863-969. Available from: https://www.ncbi.nlm.nih.gov/pubmed/17825896
  58. Shaaban, R, Zureik, M, Soussan, D, et al. Rhinitis and onset of asthma: a longitudinal population-based study. Lancet. 2008; 372: 1047-1057. Available from: https://www.ncbi.nlm.nih.gov/pubmed/18805333
  59. Holt, P. G., Sly, P. D.. Viral infections and atopy in asthma pathogenesis: new rationales for asthma prevention and treatment. Nat Med. 2012; 18: 726-735. Available from: http://www.ncbi.nlm.nih.gov/pubmed/22561836
  60. Peat, Jennifer K, Mihrshahi, Seema, Kemp, Andrew S, et al. Three-year outcomes of dietary fatty acid modification and house dust mite reduction in the Childhood Asthma Prevention Study. J Allergy Clin Immunol. 2004; 114: 807-13. Available from: https://www.ncbi.nlm.nih.gov/pubmed/15480319
  61. Marks, Guy B., Mihrshahi, Seema, Kemp, Andrew S., et al. Prevention of asthma during the first 5 years of life: a randomized controlled trial. J Allergy Clin Immunol. 2006; 118: 53-61. Available from: https://www.ncbi.nlm.nih.gov/pubmed/16815138
  62. Toelle, B. G., Garden, F. L., Ng, K. K., et al. Outcomes of the Childhood Asthma Prevention Study at 11.5 years. J Allergy Clin Immunol. 2013; 132: 1120-1222. Available from: http://www.ncbi.nlm.nih.gov/pubmed/23900055
  63. Lodrup Carlsen KC, Roll S, Carlsen KH, et al. Does pet ownership in infancy lead to asthma or allergy at school age? Pooled analysis of individual participant data from 11 European birth cohorts. PloS one. 2012; 7: e43214. Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3430634/
  64. Hehua, Z., Qing, C., Shanyan, G., et al. The impact of prenatal exposure to air pollution on childhood wheezing and asthma: A systematic review. Environ Res. 2017; 159: 519-530. Available from: https://www.ncbi.nlm.nih.gov/pubmed/28888196
  65. Jacquemin, B., Schikowski, T., Carsin, A. E., et al. The role of air pollution in adult-onset asthma: a review of the current evidence. Semin Respir Crit Care Med. 2012; 33: 606-19. Available from: https://www.ncbi.nlm.nih.gov/pubmed/22918788
  66. Mendell, M J, Mirer, A G, Cheung, K, et al. Respiratory and allergic health effects of dampness, mold, and dampness-related agents: a review of the epidemiologic evidence. Environ Health Perspect. 2011; 119: 748-756. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3114807/
  67. Tischer, C, Chen, C M, Heinrich, J. Association between domestic mould and mould components, and asthma and allergy in children: a systematic review. Eur Respir J. 2011; 38: 812-824.
  68. Lanphear, B P, Aligne, C A, Auinger, P, et al. Residential exposures associated with asthma in US children. Pediatrics. 2001; 107: 505-511. Available from: https://www.ncbi.nlm.nih.gov/pubmed/11230590
  69. Zock, J P, Plana, E, Jarvis, D, et al. The use of household cleaning sprays and adult asthma: an international longitudinal study. Am J Respir Crit Care Med. 2007; 176: 735-741. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2020829/
  70. Therapeutic Guidelines Limited. eTG Complete. Version July 2018. Therapeutic Guidelines Limited, Melbourne, 2018. Available from: https://www.tg.org.au/
  71. Dick, S., Friend, A., Dynes, K., et al. A systematic review of associations between environmental exposures and development of asthma in children aged up to 9 years. BMJ Open. 2014; 4: e006554. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/25421340
  72. Eyers, S, Weatherall, M, Jefferies, S, Beasley, R. Paracetamol in pregnancy and the risk of wheezing in offspring: a systematic review and meta-analysis. Clin Exp Allergy. 2011; 41: 482-489.
  73. Mulder, B., Schuiling-Veninga, C. C., Bos, J. H., et al. Acid-suppressive drug use in pregnancy and the toddler's asthma risk: a crossover, case-control study. J Allergy Clin Immunol. 2013; 132: 1438-40. Available from: https://www.jacionline.org/article/S0091-6749(13)01089-0/fulltext
  74. Kallen, B., Finnstrom, O., Nygren, K. G., Otterblad Olausson, P.. Maternal drug use during pregnancy and asthma risk among children. Pediatr Allergy Immunol. 2013; 24: 28-32. Available from: https://www.ncbi.nlm.nih.gov/pubmed/23331527
  75. Andersen, A. B., Erichsen, R., Farkas, D. K., et al. Prenatal exposure to acid-suppressive drugs and the risk of childhood asthma: a population-based Danish cohort study. Aliment Pharmacol Ther. 2012; 35: 1190-8. Available from: https://www.ncbi.nlm.nih.gov/pubmed/22443179
  76. Dehlink, E., Yen, E., Leichtner, A. M., et al. First evidence of a possible association between gastric acid suppression during pregnancy and childhood asthma: a population-based register study. Clin Exp Allergy. 2009; 39: 246-53. Available from: https://www.ncbi.nlm.nih.gov/pubmed/19134022
  77. Early Treatment of the Atopic Child Study Group,. Allergic factors associated with the development of asthma and the influence of cetirizine in a double-blind, randomised, placebo-controlled trial: first results of ETAC. Early Treatment of the Atopic Child. Pediatr Allergy Immunol. 1998; 9: 116-124. Available from: http://www.ncbi.nlm.nih.gov/pubmed/9814724
  78. Valovirta, E., Petersen, T. H., Piotrowska, T., et al. Results from the 5-year SQ grass sublingual immunotherapy tablet asthma prevention (GAP) trial in children with grass pollen allergy. J Allergy Clin Immunol. 2018; 141: 529-538.e13. Available from: https://www.ncbi.nlm.nih.gov/pubmed/28689794
  79. Forno, E., Young, O. M., Kumar, R., et al. Maternal obesity in pregnancy, gestational weight gain, and risk of childhood asthma. Pediatrics. 2014; 134: e535-46. Available from: https://www.ncbi.nlm.nih.gov/pubmed/25049351
  80. Egan, K. B., Ettinger, A. S., Bracken, M. B.. Childhood body mass index and subsequent physician-diagnosed asthma: a systematic review and meta-analysis of prospective cohort studies. BMC Pediatr. 2013; 13: 121. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23941287
  81. Papoutsakis, C., Priftis, K. N., Drakouli, M., et al. Childhood overweight/obesity and asthma: is there a link? A systematic review of recent epidemiologic evidence. J Acad Nutr Diet. 2013; 113: 77-105. Available from: https://www.ncbi.nlm.nih.gov/pubmed/23260726
  82. Chen, Y. C., Dong, G. H., Lin, K. C., Lee, Y. L.. Gender difference of childhood overweight and obesity in predicting the risk of incident asthma: a systematic review and meta-analysis. Obes Rev. 2013; 14: 222-31. Available from: https://www.ncbi.nlm.nih.gov/pubmed/23145849
  83. Weiler JM, Anderson SD, Randolph C, et al. Pathogenesis, prevalence, diagnosis, and management of exercise-induced bronchoconstriction: a practice parameter. Ann Allergy Asthma Immunol. 2010; 105: S1-47. Available from: http://www.ncbi.nlm.nih.gov/pubmed/21167465
  84. Fitch KD, Sue-Chu M, Anderson SD, et al. Asthma and the elite athlete: Summary of the International Olympic Committee's Consensus Conference, Lausanne, Switzerland, January 22-24, 2008. J Allergy Clin Immunol. 2008; 122: 254-260. Available from: http://www.ncbi.nlm.nih.gov/pubmed/18678340
  85. Parsons JP, Hallstrand TS, Mastronarde JG, et al. An official American Thoracic Society clinical practice guideline: exercise-induced bronchoconstriction. Am J Respir Crit Care Med. 2013; 187: 1016-27. Available from: http://www.ncbi.nlm.nih.gov/pubmed/23634861
  86. Anderson SD, Kippelen P. Airway injury as a mechanism for exercise-induced bronchoconstriction in elite athletes. J Allergy Clin Immunol. 2008; 122: 225-235. Available from: http://www.jacionline.org/article/S0091-6749(08)00785-9/fulltext
  87. Sue-Chu M, Brannan JD, Anderson SD, et al. Airway hyperresponsiveness to methacholine, adenosine5-monophosphate, mannitol, eucapnic voluntary hyperpnoea and field exercise challenge in elite cross country skiers. Brit J Sports Med. 2010; 44: 827-832. Available from: http://bjsm.bmj.com/content/44/11/827.long
  88. Bougault V, Boulet LP, Turmel J. Bronchial challenges and respiratory symptoms in elite swimmers and winter sport athletes. Chest. 2010; 138: 31S-37S. Available from: http://journal.publications.chestnet.org/article.aspx?articleid=1086631
  89. Bougault V, Turmel J, St-Laurent J, et al. Asthma, airway inflammation and epithelial damage in swimmers and cold-air athletes. Eur Respir J. 2009; 33: 740-746. Available from: http://erj.ersjournals.com/content/33/4/740.long