NA
This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Childhood asthma is a highly morbid respiratory disorder. In spite of effective remedies, heterogeneity of disease process and poor treatment compliance lead to substantial proportion of childhood asthma remaining uncontrolled. Hence, school absenteeism, loss of play hours and sleep disturbances are significant. Strain on health care budget is also high. Newer immunotherapeutic modalities do offer options for a better long-term control. But prevention is always better than cure. Since specific hygrothermal conditions and dietary factors are known to induce and sustain asthma, attention to these environmental and food factors early in life have high potential of averting and reversing the pathophysiologic process and asthma. Health education on these inducing factors and nutritional advice could greatly assist in decreasing asthma prevalence and its associated morbidity and financial costs.
Asthma is a chronic inflammatory airway disease characterized by airway hyper-responsiveness which is reversible either spontaneously or with treatment [1]. It has high individual and societal burden. It consumes a substantial fraction of a nationâs health care funds [2-5]. Direct health care costs on medical services, medicines and hospital stay constitute more than 50% of economic loss due to asthma. This expenditure on asthma is quadrupled if childâs asthma is severe enough to require hospitalizations [6, 7]. Over the years, prevalence of childhood asthma has remained high and is increasing [8-10]. Recent advances in management protocols of asthma have decreased mortality and hospitalizations in asthma but morbidity continues to be considerable [9, 10]. In view of this, more focus on prevention of asthma would be beneficial and cost-effective. Since environmental factors and dietary changes have largely contributed to this rise in prevalence of asthma, reversal of these conditions could potentially reduce development of asthma, and its morbidity in persistent disease. Primary multi-faceted preventive measures could possibly minimise emergence of asthma by 50% with similar decline in national health care expenditure on asthma.
Greater insights into pathophysiology of childhood asthma have shown that it is a heterogeneous disorder with differential response to standard treatments. Various phenotypes are recognized though the differentiation is not clear-cut. Grossly, asthma in children could be divided into atopic, non-atopic form, transient infantile wheezing and late onset childhood asthma. In the atopic type, there is a history of a close relative suffering from asthma and/or self-history of allergies of eye, nose, or skin. The symptoms start early in life and persist into adulthood with or without a symptomless phase in between. In the non-atopic type of infancy and toddler age group, the child usually wheezes with viral respiratory infections. The frequency of wheeze decreases with age and by 5-6 years, they are usually symptomless. Wheeze response to bronchodilators in them is incomplete and slow. Late onset childhood asthma type usually has an allergic basis. Typing asthma based on clinical symptoms and course, inflammometry, lung functions, genotypes and response to treatment is being attempted and could be more useful [11-14].
Environmental factors and dietary elements have been implicated in wheeze in atopic children. Innumerable aeroallergens and food allergens could initiate and sustain childhood wheeze. A host of allergens in childâs environment and excess or deficiencies of certain food factors have been found to be responsible for development of wheeze. Presence of these problems in early life of child causes a genetically predisposed child to start wheezing. Hence moderation of these factors either before or during early exposure holds promise to ward off asthma in these children.1. Environmental factors:Inhaled allergens-These could be indoor or outdoor aeroallergens. In infancy, what matters the most are the indoor allergens. 80-90% of the asthmatics are sensitised to atleast one of the common aeroallergens [15, 16]. These indoor allergens have a perennial presence in large numbers in the childâs environment. They are also small enough to be inhaled and reach the lung peripheries wherein their enzymatic degradation initiates an inflammatory process and broncho-constriction. Exposure to these allergens in early life leads to formation of memory T cells which stimulate IgE production on re-exposure to the same allergens [17]. A child exposed to heavy house dust mite load has five times more chances of having asthma than those whose environment is free of these allergens [18]. Allergen sensitization and asthma severity is directly related to the exposure levels [19-28]. High environmental humidity favours growth of these house dust mite. Heavy furnishings and upholstery offer a good microhabitat for house dust mites. Attention to these parameters while designing a house would be useful in diminishing the level of residential house dust mites. Good air exchange rate and dehumidifiers normalise air humidity and hence minimise house dust mite load in environment [19, 29-33]. Domestic pets are another source of indoor allergens. They release allergens in environment which induce and perpetuate asthma. Sensitization to the pet danders is higher in children of families with domestic pets. Chances of sensitization and subsequent asthma increase with longer contact with these animals [16, 25, 26, 34, 35]. Sensitization to other indoor allergens such as cockroach and indoor moulds is also high in children with asthma [36-38]. Grass, weeds and tree pollens are outdoor allergens which could possibly induce type I hypersensitivity in susceptible hosts and lead to development of asthma [39-41].Environmental tobacco smoke: Prenatal exposure to environmental tobacco smoke increases risk of premaurity, low birth weight and narrow airways. There are high chances of respiratory infections and airway hyperresponsiveness in such babies [42-47]. Various studies have also revealed that passive smoking in early infancy favours mechanisms which promote airway reactivity and asthma [48-50]. Elimination of this irritant in a childâs environment has the potential to decrease substantially risk of wheeze and respiratory infections.2. Allergic march:Allergic rhinitis-Allergic rhinitis and bronchial asthma are elements of the same disease process but with different symptomatology (the âunited airwaysâ concept) [51-55]. In line with âallergic marchâ, allergic rhinitis often precedes asthma and is a recognized risk factor for it [56-59]. A useful strategy to prevent asthma would be optimal management of allergic rhinitis. Treatment of allergic rhinitis decreases or delays development of asthma and halves risk of asthma-related events [60-64]. Allergen immunotherapy (AIT) or specific immunotherapy (SIT) has been found to play a promising role as disease modifying agent. Follow-up of children treated with SIT has shown that asthma development is lessened in them [63, 65-69].Atopic dermatitis-Atopic dermatitis has similarly been found to predispose to asthma [70, 71]. Prompt and adequate treatment of atopic dermatitis thwarts the onset of asthma [72].3. Dietary factors:Breastfeeding and weaning-Breastfeeding is protective against respiratory and other infections due to maternal transfer of antibodies and immune factors [73, 74]. Also, exclusive breastfeeding causes delay in introduction of cowâs milk which supposedly has 10 million times more of allergenic substances (such as ?-lactoglobulin) compared to breast milk [75, 76]. Therefore, breastfed infants are found to have less of serum IgE levels and less sensitization to various allergens [77, 78]. Atopic manifestations and asthma are also lesser in breastfed children [78, 79-82]. However, this protective association has not been consistently proven [83-85]. It is believed now that breastfeeding only protects against early wheezing and has no protective effect on asthma in older atopic children [83]. In fact, lesser infections in breastfed babies lead to rise in allergic tendency (hygiene hypothesis). There is also no role of any dietary restrictions for lactating mothers to prevent asthma and atopy in susceptible children [86]. Weaning after 4-6 months with less allergenic foods such as fruits, vegetables, cereals which are introduced one at a time is effective for asthma prevention.Food components-Fatty acids have been found to play an important role in respiratory health. Omega-3-fatty acids are protective against and omega-6 fatty acids act as promoters of airway inflammation [87, 88]. Fish oils are rich in omega-3 fatty acids and children on oily fish diets have 30-70% less chances of asthma compared to those on standard diets [89-91]. The element, sodium has been found to have an important role in regulation of smooth muscle tone. High salt intake has been found to increase airway hyper-responsiveness and asthma-related mortality [92-95]. But some studies have concluded to the contrary [96-98]. Sparrow et al and Schwartz et al found that both potassium and sodium have a direct influence on airway hyperactivity and asthma development [96, 99]. On the other hand, magnesium has a bronchodilator action [100]. A UK-based study revealed that those with impaired lung functions and higher wheeze had lower magnesium levels [101]. Thus magnesium supplementation would aid in bringing down asthma risk and asthma. Compared to standard formulas, partially hydrolyzed formulas are also found to be less allergenic with 60% more improved taste. Infants fed such special formulas were found to have 42-55% reduced risk of atopic dermatitis compared to those on standard formulas [102-105]. Addition of Lactobacillus GG to infant milk formulas has a similar negative effect on development of atopic dermatitis in children [106]. The decline in atopic dermatitis cases would simultaneously cause a similar decrease in asthma and hence such a step would have economic benefits. Vitamins A, C and E are known to possess anti-oxidant properties and can mop up oxygen-free radicals. Cellular damage and inflammation due to these radicals does not take place when levels of these vitamins in diet are sufficient. Fruits and vegetables are rich sources of these vitamins. Hence a diet deficient in fruits and vegetables increases the propensity for respiratory illnesses and wheeze [107, 108]. Strachan et al and Britton et al found that lung function parameters were lower in those with deficiency of these anti-oxidants [109, 110]. But other studies have failed to demonstrate this association [111-113]. However, vitamin D has been found to have an airway protective role and holds promise as a preventive strategy for asthma [114].4. Other infections:Mild infections in early life cause a predominant Th1 type of immune response to be activated. Since Th2 is suppressed, allergic tendency is lessened. Viruses, helminths and H.pylori infections have been studied and found to protect against allergic asthma [115-118].
Poverty, environmental dirt, microbes and psychosocial stress have been implicated in causation of asthma in poor countries [119]. The infections reduce atopy but not asthma. The non-microbicidal irritants also induce and perpetuate wheeze in such children. Attention to these factors would help eliminate and lessen chances of asthma in them.
Children with one/both parent(s) suffering from asthma/allergy, those with allergic rhinitis or atopic dermatitis, those having sensitization to one or more allergens, preterm babies, low birth weight babies and those with narrowed airways are susceptible to wheeze. Cord blood IgE levels has been found not to correlate well with asthma tendency. Children exposed to tobacco smoke in utero or early in life are also at increased risk for asthma in later life. Children who are breastfed for less than 4 months, those who have a diet deficient in anti-oxidants/omega-3 fatty acids or diet high in sodium have higher likelihood of asthma. Having known this, measures directed at overcoming these inducing factors may prove effective as preventives strategies for asthma.
Various experimental and occupational models have proven beyond doubt that environmental control measures and dietary modifications greatly assist in bringing down the prevalence of asthma [120, 121]. A controlled intervention in âat riskâ children reduced to a significant extent development of asthma [122, 123]. House dust mites proliferate in humid conditions. Hence dehumidifying the living areas could lead to a fall in house dust mite population and hence lessen likelihood of asthma. Indoor humidity should be maintained below 50%. Increasing ventilation and removal of humidifying sources in the house such as flower-pots, fish tanks, fountains would be beneficial. Proper humidity could also be achieved by balanced settings for heating and air-conditioning systems [124, 125]. House should be well aerated and sun-exposed. This will create hygrothermal conditions which will minimise house dust mite proliferation. Decarpet the house and avoid heavy upholstery, curtains and furnishings. Vacuum clean and launder the rugs well at regular intervals. Mattresses carry a heavy load of house dust mites. Sun exposure could kill them [126]. Use of dust mite protective covers for the mattresses can also reduce the allergen encumbrance and asthma risk in susceptible children. Bed-sheets should be washed regularly in hot water and preferably sundried. Pillows should be changed at frequent intervals. Soft toys in the childâs environment should be removed/lessened [127]. Anti-mite chemicals can eradicate the mites but simultaneously care should be taken to remove the dead mites and their allergens from the furnishings as these also induce asthma [128-130]. The above steps taken in early life have the potential to prevent asthma. For allergy to pet dander/hairs/secretions, restricting the entry of pets to the house especially the bedroom may help cut down the asthma risk [131]. If sensitized patient is reluctant to part with the pet, change to wooden or hard floors, adequate frequent laundering of furnishings and daily appropriate dusting of smooth surfaces and brooming/vacuuming of floors will minimise the allergen level in the atmosphere and hence asthma risk [132]. It has been seen that after a cat is removed from the house it may take as long as 6 months for the effect of the allergen avoidance to be noticeable [133]. Damp moldy areas in the house should be fixed [134]. Elimination of the environmental tobacco smoke exposure can decrease respiratory symptoms including wheeze [135]. Children with nasal/eye allergy due to pollens are benefitted with prophylactic drugs or pre-seasonal and coseasonal immunotherapy. Control of these allergies prevents asthma development [136]. Similarly, effective management of atopic dermatitis either delays or stops asthma in later life [137]. Breastfeeding for at least 4-6 months has a protective effect on asthma and wheeze-related respiratory infections [138]. Ensuring adequate amounts of recommended vitamins, minerals and essential fatty acids in diet in the long run avoids development of asthma. Supplementation with omega-3 fatty acids in âat-riskâ group reduces chances of asthma and wheeze [114, 139-141]. Since serious viral infections in infancy predispose to later wheeze, prevention of such infections with adequate care and vaccinations would be useful in prevention of asthma [142, 143].
Thus childhood asthma is multi-factorial. Various inducing factors are involved in its causation. At the same time, many environmental and dietary factors when controlled could protect against occurrence of asthma. Thus cutback of âinducersâ and augmentation of âprotectorsâ could help prevent asthma. It is no doubt a multi-pronged, tedious, time-consuming, laborious and sometimes unpredictable approach, but such preventive measures would have long-term individual, social and financial connotations. Health education and community approaches to disseminate such preventive strategies should be carried out for better success and outcomes. With successful implementation of such measures, freedom from asthma would not be an impossible dream!
1. Anon. Global strategy for asthma management and prevention. GINA report updated 2010 www.ginasthma.org2. Weiss KB, Gergen PJ, Hodgson TA. An economic evaluation of asthma in the United States New Engl J of Med 1992; 326: 862-8663. Akinbami LJ. The State of childhood asthma, Unites States, 1980-2005 Advance data From Vital and Health Statistics 2006; 381: 1-244. Hoskins G, McCowan C, Neville RG, Thomas GE, Smith B, Silverman S. Risk factors and costs associated with an asthma attack Thorax 2000; 55: 19-245. Masoli M, Fabian D, Holt S, Beasley R The global burden of asthma: executive summary of the GINA dissemination committee report. Allergy 2004; 59: 469-4786. Mellis CM, Peat JK, Bauman A, Woolcock AJ. The cost of asthma in New South Wales Med J Aust 1991; 155: 522-5287. Toelle BG, Peat JK, Mellis CM, Woolcock AJ. The cost of childhood asthma to Australian families Pediatr Pulmonol 1995; 19: 330â3358. Clark NM Community-based approaches to controlling childhood asthma. Annu Rev Public Health 2012; 33: 193-2089. Pearce N, Aït-Khaled N, Beasley R, Mallol J, Keil U, Mitchell E, Robertson C, and the ISAAC Phase Three Study Group. Worldwide trends in the prevalence of asthma symptoms: phase III of the International Study of Asthma and Allergies in Childhood (ISAAC). Thorax. 2007; 62(9): 758-76610. Akinbami LJ, Moorman JE, Bailey C, Zahran HS, King M, Johnson CA, Liu X. Trends in asthma prevalence, health care use and mortality in the United States, 2001 to 2010 NCHS Data Brief Number 94; 201211. Bel EH Clinical phenotypes of asthma Curr Opin Pulm Med 2004; 10: 44-5012. Hovland V, Riiser A, Mowinckel P, Carlsen KH, Carlsen KCL. Asthma phenotypes models in childhood: Risk factors and explanatory capacities. Am J Resp Care Crit Med 2012; 185: A408013. Agache I, Akdis C, Jutel M, Virchow JC. Untangling asthma phenotypes and endotypes Eur J Allergy and Clinical Immunol 2012; 67: 835-84614. Hesselmar B, Enelund AC, Eriksson B, Padyukov L, Hanson LA, Aberg N. The heterogeneity of asthma phenotypes in children and young adults J of Allergy Volume 2012 (2012), article ID 163089, 6 pages doi: 10.1155/2012/16308915. Burrows B, Martinez FD, Halonen M, Barbee RA, Cline MG. Association of asthma with serum IgE levels and skin test reactivity to allergens. N Engl J Med 1989; 320: 271-27716. Sears MR, Burrows B, Herbison GP, Holdaway MD, Flannery EM. Atopy in childhood. II. Relationship to airway responsiveness, hay fever and asthma. Clin Exp Allergy 1993; 23: 949â95617. Holt PG, McMenamin C, Nelson D Primary sensitisation to inhalant allergens during infancy Pediatr Allergy Immunol 1990; 1: 3-1318. Sporik R, Holgate ST, Platts-Mills TAE, Cogswell JJ. Exposure to house-dust mite allergen (Der p I) and the development of asthma in childhood: a prospective study. N Engl J Med 1990; 323: 502â50719. Peat JK, Tovey ER, Toelle BG, Haby MM, Gray EJ, Mahmic A, Woolcock AJ. House-dust mite allergens: a major risk factor for childhood asthma in Australia. Am J Respir Crit Care Med 1996; 153: 144-14620. Charpin D, Kleisbauer JP, Lanteaume A, Razzouk H, Vervloet D, Toumi M, Faraj F, Charpin J. Asthma and allergy to house-dust mites in populations living in high altitudes. Chest 1988; 93: 758-76121. Peat JK, Tovey E, Gray EJ, Mellis CM, Woolcock AJ Asthma severity and morbidity in a population sample of Sydney schoolchildren: Part II. Importance of house dust mite allergens Aust NZ J Med 1994; 24: 270-27622. Vervloet D, Charpin D, Haddi E, NâGuyen A, Birnbaum J, Soler M, van Der Brempt X. Medication requirements and house-dust mite exposure in mite-sensitive asthmatics. Allergy 1991; 46: 554-55823. Zock JP, Brunekreef B, Hazebrook-Kampschreur AAJM, Roosjen CW. House-dust mite allergen in bedroom floor dust and respiratory health of children with asthmatic symptoms. Eur Respir J 1994; 7: 1254-125924. Sporik R, Platts-Mills TAE, Cogswell JJ. Exposure to house-dust mite allergen of children admitted to hospital with asthma. Clin Exp Allergy 1993; 23: 740-74625. Gelber LE, Seltzer LH, Bouzoukis JK, Pollart SM, Chapman MD, Platts-Mills TAE. Sensitization and exposure to indoor allergens as risk factors for asthma among patients presenting to hospital. Am Rev Respir Dis 1993; 147: 573-57826. Pollart SM, Chapman MD, Fiocco GP, Rose G, Platts MT. Epidemiology of acute asthma: IgE antibodies to common inhalant allergens as a risk factor for emergency room visits. J Allergy Clin Immunol 1989; 83: 875â88227. Wickman M, Nordvall SL, Pershagen G, Sundell J, Schwartz B. House-dust mite sensitization in children and residential characteristics in a temperate region. J Allergy Clin Immunol 1991; 88: 89-9528. Bjornsson E, Norback D, Janson C, Windstrom J, Palmgren U, Strom G, Boman G Asthmatic symptoms and indoor levels of microorganisms and housedust mites. Clin Exp Allergy 1995; 25: 423-43129. Harving H, Korsgaard J, Dahl R. House-dust mite exposure reduction in specially designed, mechanically ventilated âhealthyâ homes. Allergy 1994; 49: 713-718.30. Arlian LG. Water balance and humidity requirements of house-dust mites. Exp Appl Acarol 1992; 16: 15-3531. Harving H, Korsgaard J, Dahl R. House-dust mites and associated environmental conditions in Danish homes. Allergy 1993; 48: 106-10932. Wickman M, Emenius G, Egmar A-C, Axelsson G, Pershagen G. Reduced mite allergen levels in dwellings with mechanical exhaust and supply ventilation. Clin Exp Allergy 1994; 24: 109-11433. Wickman M, Nordvall SL, Pershagen G, Korsgaard J, Johansen N, Sundell J. Mite allergens during 18 months of intervention. Allergy 1994; 49: 114-11934. Sporik R, Ingram MJ, Price W, Sussman JH, Honsinger RW, Platts-Mills TAE. Association of asthma with serum IgE and skin test reactivity to allergens among children living at high altitude: tickling the dragon's breath. Am J Respir Crit Care Med 1995; 151: 1388-139235. Desjardins A, Benoit C, Ghezzo H, LâArcheveque J, LeBlanc C, Paquette L, Cartier A, Malo JL. Exposure to domestic animals and risk of immunologic sensitization in subjects with asthma. J Allergy Clin Immunol 1993; 91: 979-98636. Lee MF, Song PP, Hwang GY, Lin SJ, Chen YH. Sensitization to Per a 2 of the American cockroach correlates with more clinical severity among airway allergic patients in Taiwan. Ann Allergy Asthma Immunol 2012; 108: 243-24837. OâDriscoll BR, Hopkinson LC, Denning DW. Mold sensitization is common amongst patients with severe asthma requiring multiple hospital admissions BMC Pulmonary Medicine 2005; 5: 4 doi:10.1186/1471-2466-5-438. Warner JA, Little SA, Pollock I, Longbottom JL, Warner JO. The influence of exposure to house-dust mite, cat pollen and fungal allergens in the home on primary sensitisation in asthma. Pediatr Allergy Immunol 1990; 1: 79-8639. Bellomo R, Gigliotti P, Treloar A, Holmes P, Suphioglu C, Singh MB Two consecutive thunderstorm-associated epidemics of asthma in the city of Melbourne. The possible role of rye grass pollen. Med J Aust 1992; 156: 834-83740. Suphioglu C, Singh MB, Taylor P, Bellomo R, Holmes P, Puy R, Knox RB Mechanism of grass pollen-induced asthma. Lancet 1992; 339 569-57241. Peat JK, Tovey E, Mellis CM, Leeder SR, Woolcock AJ. Importance of house dust mite and Alternaria allergens in childhood asthma: an epidemiological study in two climatic regions of Australia. Clin Exp Allergy 1993; 23: 812-82042. Chen Y. Environmental tobacco smoke, low birth weight, and hospitalization for respiratory disease Am J Respir Crit Care Med 1994; 150: 54-5843. Conter V, Cortinovis I, Rogari P, Riva L Weight growth in infants born to mothers who smoked during pregnancy BMJ 1995; 310: 768-77144. Martinez FD, Morgan WJ, Wright AL, Holberg CJ, Taussig LM Diminished lung function as a predisposing factor for wheezing respiratory illness in infants. N Engl J Med 1988; 319: 1112-111745. Frischer T, Kuehr J, Meinert R, Karmaus W, Barth R, Hermann-Kunz E, Urbanek R Relationship between low birth weight and respiratory symptoms in a cohort of primary school children. Acta Paediatr 1992; 81: 1040-104146. Kitchen WH, Olinsky A, Doyle LW, Ford GW, Murton LJ, Slonim L, Callanan C. Respiratory health and lung function in 8 year old children of very low birth weight: a cohort study. Pediatr 1992; 89: 1151-115847. Giffin F, Greenough A, Yuksel B. Relationship between lung function results in the first year of life and respiratory morbidity in early childhood in patients born prematurely Pediatr Pulmonol 1994; 18: 290-29448. Rylander E, Pershagen G, Eriksson M, Nordvall L. Parental smoking and other risk factors for wheezing bronchitis in children. Eur J Epidemiol 1993; 9: 517-52649. Lai Y-L, Thacker A, Gairola CG. Sidestream cigarette smoke exposure and airway reactivity during early life. J Appl Physiol 1994; 77: 1868-187450. Joad JP, Bric JM, Kott KS. Effects of chronic side-stream smoke exposure in utero and/or postnatally on airway function and reactivity to methacholine in rats. Am J Respir Crit Care Med 1994; 149: A39251. Togias A. Mechanisms of nose-lung interaction. Allergy 1999; 54: 94-10552. Passalacqua G, Ciprandi G, Canonica GW. United airways disease: therapeutic aspects. Thorax 2000; 55: S26-2753. Passalacqua G, Ciprandi G, Canonica GW. The nose-lung interaction in allergic rhinitis and asthma: united airways disease Curr Opin Allergy Clin Immunol 2001; 1: 7-1354. Rimmer J, Ruhno JW. 6: Rhinitis and asthma: united airways disease. Med J Aus 2006; 185: 565-57155. Compalati E, Ridolo E, Passalacqua G, Braido F, Villa E, Canonica GW. The link between allergic rhinitis and asthma: the united airways disease. Expert Rev Clin Immunol 2010; 6: 413-42356. Burgess JA, Walter EH, Brynes GB, Matheson MC, Jenkins MA, Wharton CL, Johns DP, Abramson MJ, Hopper JL, Dharmage SC Childhood allergic rhinitis predicts asthma incidence and persistence to middle age: a longitudinal study. J Allergy Clin Immunol 2007; 120: 863-86957. Shaaban R, Zureik M, Soussan D, Neukirch C, Heinrich J, Sunyer J, Wjst M, Cerveri I, Pin I, Bousquet J, Jarvis D, Burney PG, Neukirch F, Leynaert B. Rhinitis and onset of asthma: a longitudinal population-based study. Lancet 2008; 372: 1049-105758. Linna O, Kokkonen J, Lukin M. A 10-year prognosis for childhood allergic rhinitis. Acta Pediatr 1992; 81: 100-10259. Guerra S, Sherill DL, Martinez FD, Barbee RA. Rhinitis as an independent risk factor for adult-onset asthma. J Allergy Clin Immunol 2002; 109: 419-42560. Wahn U. 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: 116-12461. Foresi A, Pelucchi A, Gherson G, Mastropasqua G, Chiapparino A, Tesli R Once daily intranasal fluticasone propionate (200 micrograms) reduces nasal symptoms and inflammation but also attenuates the increase in bronchial responsiveness during the pollen season in allergic rhinitis. J Allergy Clin Immunol 1996; 98: 274-28262. Guilbert TW, Morgan WJ, Zeiger RS, Mauger DT, Boehmer SJ, Szefler SJ, Bacharier LB, Lemanske RF Jr., Strunk RC, Allen DB, Bloomberg GR, Heldt G, Krawiec M, Larsen G, Liu AH, Chinchilli VM, Sorkness CA, Taussig LM, Martinez FD Long-term inhaled corticosteroids in preschool children at high risk for asthma. N Engl J Med 2006; 354: 1985-199763. Fiocchi A, Fox AT. Preventing progression of allergic rhinitis: the role of specific immunotherapy. Arch Dis Child Educ Pract Ed 2011; 96: 91-10064. Crystal-Peters J, Neslusan C, Crown WH, Torres A Treating allergic rhinitis in patients with comorbid asthma: the risk of asthma-related hospitalizations and emergency department visits. J Allergy Clin Immunol 2002; 109: 57-6265. Cui ZH, Radinger M, Sjostrand M, Lotvall J. Repeated allergen exposure reduce early phase airway response and leukotriene release despite upregulation of 5-lipoxygenase pathways. Clinical and translational allergy 2012; 2: 7-1866. Niggermann B, Jacobsen L, Dreborg S, Ferdousi HA, Haiken S, Host A, Koivikko A, Koller D, Norberg LA, Urbanek R, Valovirta E, Wahn U, Moller C, Pat investigator group. Five-year follow-up on the PAT study: specific immunotherapy and long-term prevention of asthma in children. Allergy 2006; 61: 855-85967. Moller C, Dreborg S, Ferdousi HA, Halken S, Host A, Jacobsen L, Koivikko A, Koller DY, Niggemann B, Norberg LA, Urbanek R, Valovirta E, Wahn U Pollen immunotherapy reduces the development of asthma in children with seasonal rhinoconjunctivitis. J Allergy Clin Immunol 2002; 109: 251-25668. Jacobsen L, Niggermann B, Dreborg S, Ferdousi HA, Halken S, Host A, Koivikko A, Norberg LA, Valovirta E, Wahn U, Moller C. Specific immunotherapy has long-term preventive effect of seasonal and perennial asthma: 10 year follow-up on the PAT study. Allergy 2007; 62: 943-94869. Polosa R, Li Gotti F, Mangano G, Piolino G, Mastruzzo G, Vancheri C, Lisitano N, Crimi N. Effect of immunotherapy on asthma progression, BHR and sputum eosinophils in allergic rhinitis. Allergy 2004; 59: 1224-122870. Spergel JM, Paller AS. Atopic dermatitis and the atopic march J Allergy Clin Immunol 2003; 112: S118-S12771. Zheng T, Yu J, Oh MH, Zhu Z. The atopic march: Progression from atopic dermatitis to allergic rhinitis and asthma. Allergy Asthma Immunol Res 2011; 3: 67-7372. Warner JO, ETAC Study Group. Early treatment of the atopic child. A double-blinded, randomized, placebo-controlled trial of cetirizine in preventing the onset of asthma in children with atopic dermatitis: 18 monthsâ treatment and 18 monthsâ posttreatment follow-up. J Allergy Clin Immunol 2001; 108: 929-93773. Oddy WH. A review of the effects of breastfeeding on respiratory infections, atopy and childhood asthma J Asthma 2004; 41: 605-62174. Woodward A, Douglas RM, Graham NMH, Miles H. Acute respiratory illness in Adelaide children: breastfeeding modifies the effect of passive smoking. J Epidemiol Commun Health 1990; 44: 224-23075. Kuitunen M, Savilahi E, Sarnesto A. Human lactalbumin ad bovine ?-lactoglobulin absorption in infants. Allergy 1994; 49: 354-36076. Gdalevich M, Mimouni D, David M, Mimouni M. Breastfeeding and the onset of atopic dermatitis in childhood: a systemic review and meta-analysis of prospective studies. J Am Acad Dermatol 2001; 45: 520-52777. Buonocore G, Zani S, Tomasini B, Tripodi V, Grano S, Bracci R. Serum IgE concentrations in the neonatal period. Biol Neonate 1992; 62: 10-1478. Oddy WH, Holt PG, Sly PD, Read AW, Landau LI, Stanley FJ, Kendall GE, Burton PR. Association between breast feeding and asthma in 6 year old children: findings of a prospective birth cohort study. BMJ 1999; 319:815-81979. Businco L, Marchetti F, Pellegrini G, Cantani A, Perlini R. Prevention of atopic disease in âat-risk newbornsâ by prolonged breast-feeding. Ann Allergy 1983; 51: 296-29980. Bardare M, Vaccari A, Allievi E, Brunelli L, Coco F, de Gaspari GC, Flauto U. Influence of dietary manipulation on incidence of atopic disease in infants at risk. Ann Allergy 1993; 71: 366-37181. Saarinen UM, Kajosari M. Breast-feeding as prophylaxis against atopic disease: prospective follow-up study until 17 years old. Lancet 1995; 346: 1065â106982. Oddy WH, Peat JK, De Klerk NH. Maternal Asthma, infant feeding, and the risk of asthma in childhood J Allergy Clin Immunol 2002; 110: 65-6783. Williams M. Prevention strategies for asthma-primary prevention. CMAJ 2005; 173: S20-S2484. Wright AL, Holberg CJ, Taussig LM, Martinez FD. Factors influencing the relation of infant feeding to asthma and recurrent wheeze in childhood. Thorax 2001; 56 (3):192-19785. Sears MR, Greene JM, Willan AR, Taylor DR, Flannery EM, Cowan JO, Herbison GP, Poulton R. Long-term relation between breastfeeding and development of atopy and asthma in children and young adults: a longitudinal study. Lancet 2002; 360(9337): 901-90786. Greer FR, Sicherer SH, Burks AW, American Academy of Pediatrics Committee on Nutrition, American Academy of Pediatrics Section on Allergy and Immunology. Effects of early interventions on the development of atopic disease in infants and children; the role of maternal dietary restriction, breastfeeding, timing of introduction of complementary foods, and hydrolysed formulas. Pediatrics 2008; 121: 183-19187. Ritter JM, Taylor GW. Fish oil in asthma. Thorax 1988; 43: 81-8388. Anandan C, Nurmatov U, Sheikh A. Omega 3 and 6 oils for primary prevention of allergic disease: systematic review and meta-analysis Allergy 2009; 64(6): 840-889. Peat JK, Salome CM, Woolcock AJ. Factors associated with bronchial hyperresponsiveness in Australian adults and children. Eur Respir J 1992; 5: 921-92990. Hodge L, Salome CM, Peat JK, Haby MM, Xuan W, Woolcock AJ. Consumption of oily fish and childhood asthma risk. Med J Aust 1996; 164: 137-14091. Schwartz J, Weiss ST. The relationship of dietary fish intake to level of pulmonary function in the first National Health and Nutrition Examination Survey (NHANES 1). Eur Respir J 1994; 7: 1821-182492. Burney P. A diet rich in sodium may potentiate asthma: epidemiological evidence for a new hypothesis. Chest 1987; 91 (Suppl.): 143Sâ148S93. Burney PGJ, Britton JR, Chinn S, Tattersfield AE, Platt HS, Papacosta AO, Kelson MC. Response to inhaled histamine and 24 hour sodium excretion. BMJ 1986; 292: 1483-148694. Pistelli R, Forastiere F, Corbo GM, Dellâ Orco V, Brancato G, Agabiti N, Pizzabiocca A, Perucci CA. Respiratory symptoms and bronchial responsiveness are related to dietary salt intake and urinary potassium excretion in male children. Eur Respir J 1993; 6: 517-52295. Tribe RM, Barton JR, Poston L, Burney PGJ. Dietary sodium intake, airway responsiveness, and cellular sodium transport. Am J Respir Crit Care Med 1994; 149: 1426â143396. Sparrow D, O'Connor GT, Rosner B, Weiss ST. Methacholine airway responsiveness and 24 hour urine excretion of sodium and potassium: the normative aging study. Am Rev Respir Dis 1991; 144: 722â72597. Devereux G, Beach JR, Bromly C, Avery AJ, Ayatollahi SM, Williams SM, Stenton SC, Bourke SJ, Hendrick DJ Effect of dietary sodium on airways responsiveness and its importance in the epidemiology of asthma: an evaluation in three areas of northern England. Thorax 1995; 50: 941-94798. Britton J, Pavord I, Richards K, Knox A, Wisniewski A, Weiss S, Tattersfield A. Dietary sodium intake and the risk of airway hyperreactivity in a random adult population. Thorax 1994; 49: 875-88099. Schwartz J, Weiss ST. Dietary factors and their relation to respiratory symptoms: the second National Health and Nutrition Examination survey. Am J Epid 1990; 132: 67-76100. Freeman NCG, Dona S, McGarvey P. Magnesium may mean breathing easier. Environmental nutrition 1995; 18 (4): 7101. Britton J, Pavord I, Richards K, Wisniewski A, Knox A, Lewis S, Tattersfield A, Weiss S. Dietary magnesium, lung function, wheezing, and airway hyperreactivity in a random adult population sample. Lancet 1994; 344: 357-362102. von Berg A, Koletzko S, Grubl A, Filipiak-Pittroff B, Wichmann HE, Bauer CP, Reinhardt D, Berdel D, German Infant Nutritional Intervention Study Group. The effect of hydrolyzed cowâs milk formula for allergy prevention in the first year of life: the German Infant Nutritional Intervention Study, a randomized double-blind trial. J Allergy Clin Immunol 2003; 111: 533-540103. Szajewska H, Horvath A Meta-analysis of the evidence for a partially hydrolyzed 100% whey formula for the prevention of allergic diseases. Curr Med Res Opin 2010; 26: 423-437104. Alexander DD, Cabana MD. Partially hydrolyzed 100% whey protein infant formula and reduced risk of atopic dermatitis: a meta-analysis. JPGN 2010; 50: 422-430105. von Berg A, Filipiak-Pittroff B, Kramer U, Link E, Bollrath C, Brockow I, Koletzko S, Grubl A, Heinrich J, Wichmann HE, Bauer CP, Reinhardt D, Berdel D Preventive effect of hydrolyzed infant formulas persists until age 6 years: long-term results from the German Infant Nutritional Intervention Study (GINI). J Allergy Clin Immunol 2008; 121: 1442-1447106. Canani RB, Nocerino R, Terrin G, Coruzzo A, Cosenza L, Leone L, Troncone R. Effect of Lactobacillus GG on tolerance acquisition in infants with cowâs milk allergy: A randomized trial. J Allergy and Clinical Immunology. Doi: 10.1016/j.jaci.2011.10.004107. Wright Y. Eat apples, avoid asthma. Australian table 2003; 4 (10): 19108. McKeever TM, Britton J Diet and asthma. Am J Respir Crit Care Med 2004; 170: 725-729109. Strachan D, Cox BD, Erzinclioglu SW, Walters DE, Whichelow MJ. Ventilatory function and winter fresh fruit consumption in a random sample of British adults. Thorax 1991; 46: 624-629110. Britton JR, Pavord ID, Richards KA, Knox AJ, Wisniewski AF, Lewis SA, Tattersfield AE, Weiss ST. Dietary antioxidant vitamin intake and lung function in the general population. Am J Respir Crit Care Med 1995; 151: 1383-1387111. Shahar E, Folsom AR, Melnick SL, Tockman MS, Comstock GW, Shimakawa T, Higgins MW, Sorlie PD, Szklo M. Does dietary vitamin A protect against airway obstruction? Am J Respir Crit Care Med 1994; 150: 978-982112. Miedema I, Feskens EJM, Heederik D, Kromhout D. Dietary determinants of long-term incidence of chronic nonspecific lung diseases. Am J Epid 1993; 138: 37â45113. Troisi RJ, Willett WC, Weiss ST, Trichopoulos D, Rosner B, Speizer FE. A prospective study of diet and adultonset asthma. Am J Respir Crit Care Med 1995; 151: 1401â1408114. Litonjua AA. Fat-soluble vitamins and atopic disease: what is the evidence? Proc Nutr Soc 2012; 71: 67-74115. Kitagaki K, Businga TR, Racila D, Elliott DE, Weinstock JV, Kline JN. Intestinal helminths protect in a murne model of asthma J Immunol 2006; 177: 1628-1635116. Wilson MS, Taylor MD, Balic A, Finney CA, Lamb JR, Maizels RM. Suppression of allergic airway inflammation by helminth-induced regulatory T cells J Exp Med 2005; 202: 1199-1212117. Chang YJ et al Influenza infection in suckling mice expands an NKT cell subset that protects against airway hyperreactivity J Clin Invest 2011; 121(1): 57-69.118. Arnold IC, Dehzad N, Reuter S, Martin H, Becher B, Taube C, Mulle A. Helicbacter pylori infection prevents allergic asthma in mouse models through the induction of regulatory T cells J Clin Invest 2011; 121: 3088-3093119. Cooper PJ, Rodriques LC, Barreto ML. Influence of poverty and infection on asthma in Latin America. Curr Opin Allergy Clin Immunol 2012; 12: 171-178120. Anto JM, Sunyer J, Reed CE, Sabria J, Martinez F, Morell F, Codina R, Rodriguez-Roisin R, Rodrigo MJ, Roca J, Saez M. Preventing asthma epidemics due to soybeans by dust control measures. N Engl J Med 1993; 329: 1760-1763121. Chan-Yeung K, Barton G, MacLean L, Grzyowski S. Occupational asthma and rhinitis due to western red cedar. Am Rev Respir Dis 1973; 108: 1094-1102122. Arshad SH, Matthews S, Gant C, Hide DW. Effect of allergen avoidance on development of allergic disorders in infancy. Lancet 1992; 339: 1493-1497123. Hide DW, Matthews S, Matthews L, Stevens M, Ridout S, Twiselton R, Grant C, Arshad SH. Effect of allergen avoidance in infancy on allergic manifestations at age two years. J Allergy Clin Immunol 1994; 93: 842-846124. Cabrera P, Julia-Serda G, Rodriguez de Castro F, Caminero J, Barber D, Carrillo T. Reduction of house-dust mite allergens after dehumidifier use. J Allergy Clin Immunol 1995; 95: 635-636125. Tovey E. House-dust control measures: are they worthwhile? Mod Med Aust 1993; August: 118-127126. Eggleston PA, Bush RK. Environmental allergen avoidance: An overview Journal of Allergy and Clinical Immunology 2001; 107 (3): S403-S440127. Platts-Mills TAE, Vaughan JW, Carter MC, Woodfolk JA The role of intervention in established allergy: Avoidance of indoor allergens in the treatment of chronic allergic disease. J Allergy Clinical Immunology 2000; 106 (5): 787-804128. Woodfolk JA, Hayden ML, Miller JD, Rose G, Chapman MD, Platts-Mills TAE. Chemical treatment of carpets to reduce allergen: a detailed study of the effects of tannic acid on indoor allergens. J Allergy Clin Immunol 1994; 94: 19-26129. Tovey ER, Marks GB, Matthews M, Woolcock AJ. Changes in mite allergen Der p I in house-dust following spraying with tannic acid/acaricide solution Clin Exp Allergy 1992; 22: 67-74130. Huss RW, Huss K, Squire EN, Carpenter GB, Smith LJ, Salata K, Hershey J Mite allergen control with acaricide fails. J Allergy Clin Immunol 1994; 94: 27-32131. Wood RA, Chapman MD, Adkinson NF, Eggleston PA The effect of cat removal on allergen content in household dust samples. J Allergy Clin Immunol 1989; 83: 730-734132. Arlian LG, Neal JS, Morgan MS, Rapp CM, Clobes AL. Distribution and removal of cat, dog and mite allergens on smooth surfaces in homes with and without pets Ann Allergy Asthma Immunol 2001; 87 (4): 296-302133. Peat JK. Prevention of asthma Eur Resp J. 1996; 9: 1545-1555134. Bornehag CG, Sundell J, Sigsgaard T. Dampness in buildings and health (DBH): Report from an ongoing epidemiological investigation on the association between indoor environmental factors and health effects among children in Sweden. Indoor Air 2004; 14 Supplement 7: 59-66135. Eisner MD, Yelin EH, Henke J, Shiboski SC, Blanc PD Environmental tobacco smoke and adult asthma: the impact of changing exposure status on health outcomes. Am J Respir Crit Care Med 1998;158:170-175136. Novembre E, Galli E, Landi F, Caffarelli C, Pifferi M, De Marco E, Burastero SE, Calori G, Benetti L, Bonazza P, Puccinelli P, Parmiani S, Bernardini R, Vierucci A. Coseasonal sublingual immunotherapy reduces the development of asthma in children with allergic rhinoconjunctivitis J Allergy Clin Immunol 2004; 114 (4): 851-857137. Galli E, Gianni S, Auricchio G, Brunetti E, Mancino G, Rossi P Atopic dermatitis and asthma Allergy Asthma Proc. 2007; 28(5): 540-543138. Duijts L, Jaddoe VWV, Hofman A, Moll HA. Prolonged and exclusive breastfeeding reduces the risk of infectious diseases in infancy Pediatrics 2010; 1: e18-e25139. Dry J, Vincent D. Effects of fish oil diet on asthma: results of a 10 year double-blind study. Arch Appl Immunol 1991; 95: 156-157140. Carey OJ, Locke C, Cookson JB. Effect of alterations of dietary sodium on the severity of asthma in men. Thorax 1993; 48: 714-718141. Burney PGJ, Neild JE, Twort CHC, Chinn S, Jones TD, Mitchell WD, Bateman C, Cameron IR Effect of changing dietary sodium on the airway response to histamine. Thorax 1989; 44: 36-41142. Simoes EAF. Treatment and prevention of respiratory syncytial virus lower respiratory tract infection. Am J Respir Crit Care Med 2001, 163: S14-S17143. Kimpen JLL. Prevention and treatment of respiratory syncytial virus bronchioloitis and postbronchiolitis wheezing Respiratory Research 2002; 3: S40-S45