Viral Initially Allergy and Asthma
Widodo Judarwanto. Children Allergy Center Jakarta Indonesia.
Viral respiratory tract infections are important respiratory pathogens implicated in allergy exacerbations such as asthma, dermatitis, allergy gastrointestinal and other manifestation. The etiology and morbidity associated with allergy and asthma are thought to stem from both genetic factors and potentially modifiable environmental factors, such as viral infections. Although it is unclear whether respiratory viral infections initially allergy and asthma, observational studies have demonstrated a high rate of allergy and asthma in children with a history of severe viral lower respiratory tract infections during infancy, and viruses are associated with the majority of asthma exacerbations among both children and adults.
The possible role of viral infections in the inception of asthma has been the matter of considerable debate. Older data suggested that viral respiratory infections occurring during early life could alter the lungs and the immune system, thus starting the process leading to allergic sensitization and persistent bronchial responsiveness. More recent studies suggest that infants who wheeze belong to two distinct groups, which at present can only be differentiated by the evolution of their illness. Most of these infants have a transitory tendency to wheeze during viral infections, and their lung function shortly after birth is significantly lower than that of infants who will not wheeze during similar infections. Most of these children become symptom-free during the preschool years, and their condition is not associated with higher serum IgE levels. A smaller group of children who wheeze as infants will still have wheezing episodes during the early school years. The factors that determine which infants will become persistent wheezers are not well understood, but viral infections per se are likely to play a minor role, if any. Early sensitization to aeroallergens in subjects genetically predisposed to having high serum IgE levels seems to be the main risk factor for this condition.
Viruses are recognized to be the major cause of respiratory infections. Clinical and experimental evidence also supports an important role for viruses in the pathogenesis of lower airway disease and asthma exacerbation. In prospective epidemiological studies, 80% of asthma exacerbations in school-aged children and half of all asthma exacerbations in adults have been associated with viral upper respiratory infections. Human rhinovirus (HRV) has been implicated as the principal virus associated with asthma exacerbation. In our studies on respiratory viruses, we have observed two clinical patterns of presentation. The viruses can either be a precipitating factor of respiratory illness characterized by a typical clinical onset, or can induce an atypical clinical onset such as haemoptysis, pleuritis, spontaneous pneumothorax and asthmatic syndrome. Thus the observed clinicoradiological and functional features during atypical viral respiratory infection may be correlated to the long-term biological effects induced by previous and concurrent infections.
The impact of respiratory viral infection on wheezing illnesses and asthma exacerbations
Patients at risk of asthma, or with existing asthma, viral respiratory tract infections can have a profound effect on the expression of disease or loss of control. New evidence has shown that wheezing episodes early in life due to human rhinoviruses are a major risk factor for the later diagnosis of asthma at age 6 years. For those with existing asthma, exacerbations are a major cause of morbidity, can need acute care, and can, albeit rarely, result in death.
Viral respiratory tract infections, predominantly those caused by human rhinoviruses, are associated with asthma exacerbations. Respiratory viral infections profoundly influence the disease activity of wheezing illnesses and asthma in early childhood. Viral bronchiolitis shares many features with asthma and a subset of children develop recurrent wheezing after their initial illness. Recently mechanisms for virus-induced exacerbations of childhood asthma are beginning to be focused on and defined. Viruses cause systemic immune activation and also produce local inflammation. These factors are likely to affect airway pathogenesis leading to airway narrowing, an increase in mucus production, and eventually bronchospasm, and airway obstruction. These new insights related to the pathogenesis and disease activity are likely to provide new targets for the therapy and prevention of early asthma in childhood.
The effects of respiratory viral infection on airway reactivity are multiple. Although virus-associated changes are many, we have at present no evidence to show that respiratory viruses cause intrinsic abnormalities in airway smooth muscle function. Rather, respiratory viruses influence bronchial smooth muscle function through a variety of other means: epithelial injury, PMN-dependent inflammation, and greater mediator release. These observations suggest that a common pathway to development of airway hyperreactivity during respiratory viral illnesses is to enhance those factors which participate in the inflammatory response. When the target of this enhanced inflammatory response becomes the airway, greater bronchial reactivity and obstruction result. Although many questions remain to be answered, we feel that future studies to evaluate the biology of respiratory virus effects on mechanisms of airway responsiveness will lead to a greater understanding of asthma pathogenesis.
There is also evidence that deficiencies in antiviral activity and the integrity of the airway epithelial barrier could make individuals with asthma more likely to have severe viral respiratory infections of the lower airway, and thus increase the risk of exacerbation. In view of the effect of respiratory viruses on many aspects of asthma, efforts to understand the mechanisms and risk factors by which these airway infections cause changes in airway pathophysiology are a first step towards improved treatment.
Respiratory syncytial virus (RSV) is the most important cause of viral lower respiratory tract disease in infants and children worldwide and the most common cause of childhood hospitalization in high-income countries. In industrialized countries, the rates of RSV hospitalization have been increasing, and, likewise, an increase in atopic disease has been reported.
In prospective cohort studies, RSV bronchiolitis during infancy or in the first 3 years of life has been found to be an important risk factor for the development of subsequent wheezing and asthma in the ensuing 7 to 11 years, and a causal relation between RSV hospitalization and subsequent hypersensitive airways has been suggested. However, it has also been suggested that a family history of atopy may dispose infants to develop more serious RSV lower respiratory tract infections (LRIs), and studies have shown that a parental history of asthma, especially on the maternal side, increases the risk of developing LRI in early life. It is still unclear, however, whether RSV LRI is causal in the development of subsequent recurrent wheezing and asthma or whether severe RSV LRI occurs on the background of an atopic predisposition and/or hypersensitive airways. The present study examined whether atopic disposition, wheezing, and atopic disorders were determinants for subsequent RSV hospitalization.
The role of respiratory viral infection in the development of asthma remains unclear. A number of factors play crucial roles, including the type of virus, the severity of the disease, the time of the infection, and, most important, the host predisposition. On the other hand, there is little doubt that a strong association exists between viral respiratory infections and induction of wheezing illnesses and asthma exacerbations. The underlying mechanisms, although not fully clarified, are likely to be multifactorial, involving inflammation of the bronchial mucosa, which interacts under certain circumstances with allergic inflammation. In addition, repetitive infections play an important role in perpetuating inflammation and airway hyperresponsiveness, especially in the presence of atopy, leading from childhood asthma to a more persistent asthma phenotype.
The mechanisms by which Viral respiratory tract infections trigger inflammatory responses in the lower airway are poorly understood, in particular their ability to infect the lower airway. Bronchial inflammatory cell (lymphocyte and eosinophil) recruitment has been demonstrated. IL-8 is a potent proinflammatory chemokine that is chemotactic for neutrophils, lymphocytes, eosinophils, and monocytes and may be important in the pathogenesis of virus-induced asthma. Increased levels of IL-8 have been found in nasal samples in natural and experimental rhinovirus infections. In these studies we therefore examine the ability of rhinovirus to infect a transformed lower airway epithelial cell line (A549) and to induce IL-8 protein release and mRNA induction. We observed that rhinovirus type 9 is able to undergo full viral replication in A549 cells, and peak viral titers were found 24 h after inoculation. Rhinovirus infection induced a dose- and time-dependent IL-8 release up to 5 days after infection and an increase in IL-8 mRNA expression that was maximal between 3 and 24 h after infection. UV inactivation of the virus completely inhibited replication, but only reduced IL-8 protein production and mRNA induction by half, while prevention of virus-receptor binding completely inhibited virus-induced IL-8 release, suggesting that part of the observed effects was due to viral replication and part was due to virus-receptor binding. These studies demonstrate that rhinoviruses are capable of infecting a pulmonary epithelial cell line and inducing IL-8 release. These findings may be important in understanding the pathogenesis of rhinovirus-induced asthma exacerbations.
Acute viral infection results in increased airway responsiveness to inhaled methacholine and pulmonary neutrophilic and eosinophilic inflammation. This response is associated with predominant production of Th-1-type cytokines in peribronchial lymph node cells in vitro. Mice sensitized to ovalbumin via the airways after RSV infection developed increased airway responsiveness to methacholine and pulmonary eosinophilic and neutrophilic inflammation, associated with the predominant production of Th-2-type cytokines. Treatment of the mice with anti-IL-5 antibody abolished airway hyperresponsiveness and eosinophilic but not neutrophilic inflammation in both acutely infected mice and mice sensitized after infection.
To address the role of IL-11 in viral airways dysfunction, we determined whether infectious agents that exacerbate asthma stimulate stromal cell IL-11 production, determined whether IL-11 could be detected at sites of viral infection and evaluated the effects of IL-11 on airway physiology. Respiratory syncytial virus (RSV), parainfluenza virus type 3 (PIV3), and rhinovirus (RV) 14 were potent stimulators while cytomegalovirus and adenovirus only weakly stimulated and herpes simplex virus type 2 and bacteria did not stimulate IL-11 elaboration. IL-11 was not detected or barely detected in nasal aspirates from children without, but was detected in aspirates from children with viral upper respiratory tract infections. The levels of IL-11 were highest in patients with clinically detectable wheezing. IL-11 also caused nonspecific airways hyperresponsiveness in BALB/c mice. These studies demonstrate that three major causes of viral-induced asthma, RSV, RV, and PIV, in contrast to other viruses and bacteria, share the ability to induce stromal cell IL-11 production. They also demonstrate that IL-11 can be detected in vivo during viral respiratory infections, that the presence of IL-11 correlates with clinical bronchospasm and that IL-11 is a potent inducer of airways hyperresponsiveness. IL-11 may be an important mediator in viral airways disorders.
Respiratory viral infections are very important triggers of asthma exacerbation. Recent epidemiologic studies support the hypothesis that they are associated with 80 to 85% of acute attacks of asthma in children. The respiratory syncytial and parainfluenza viruses are predominantly detected in infants, while rhinovirus and mycoplasma are the commonest in children. In practice for anallergy and asthmatic child, it is necessary: 1. to vaccinate against influenza; 2. resume or increase the inhaled antiinflammatory therapeutics in moderate to severe asthma, before the viral epidemic season; 3. teach the child and his family on the attitude to have during an upper respiratory infection and when to visit a physician.
- Busse WW, Lemanske RF Jr, Gern JE. Role of viral respiratory infections in asthma and asthma exacerbations. Lancet. 2010 Sep 4;376(9743):826-34.
- Oh JW. Respiratory viral infections and early asthma in childhood. Allergol Int. 2006 Dec;55(4):369-72.
- Busse WW. The contribution of viral respiratory infections to the pathogenesis of airway hyperreactivity. Chest. 1988 May;93(5):1076-82.
- Carroll KN, Hartert TV. The impact of respiratory viral infection on wheezing illnesses and asthma exacerbations. Immunol Allergy Clin North Am. 2008 Aug;28(3):539-61, viii.
- Micillo E, Marcatili P, Palmieri S, Mazzarella G. Viruses and Asthmatic Syndromes. Monaldi Archives for Chest Disease 53(1):88-91, 1998 Feb
- Schwarze J, Hamelmann E, Bradley KL, Takeda K, Gelfand EW. Respiratory Syncytial Virus Infection Results in Airway Hyperresponsiveness and Enhanced Airway Sensitization to Allergen. Journal of Clinical Investigation 100(1):226-33, 1997 Jul 1
- Velissariou IM, Papadopoulos NG. The role of respiratory viruses in the pathogenesis of pediatric asthma. Pediatr Ann. 2006 Sep;35(9):637-42.
- Refabert L, Mahut B, de Blic J, Scheinmann P. Acute Viral Respiratory Infections and Asthma. Revue du Praticien 46(17):2077-82, 1996 Nov 1
- Nystad W, Skrondal A, Magnus P. Day care attendance, recurrent respiratory tract infections and asthma. Int J Epidemiol. 1999;28 :882 –887[Abstract/Free Full Text]
- Martinez FD. Viral Infections and the Development of Asthma. American Journal of Respiratory & Critical Care Medicine 151(5):1644-7; discussion 1647-8, 1995 May
- Einarsson O, Geba GP, Zhu Z, Landry M, Elias JA. In Vivo and In Vitro by Respiratory Viruses and Induction of Airways Hyperresponsiveness Journal of Clinical Investigation 97(4):915-24, 1996 Feb 15
- Stamwell-Smith R, Bloomfield S. The hygiene hypothesis and implications for home hygiene, International Scientific Forum on Home Hygiene, Milan, 2004. Available at: www.ifh-homehygiene.org/2003/2hypothesis/hh.htm
- Balemans WAF, Rovers MM, Cornelis K. Childhood upper respiratory tract infections are not associated with asthma, hay fever and eczema at adulthood: a birth cohort study [abstract]. Eur Respir J. 2004;24(suppl 48) :4046
- Nicolai T, von Mutius E. Risk of asthma in children with a history of croup. Acta Paediatr. 1996;85 :1295 –1299[Web of Science][Medline]
- Grimfeld A. The Wheezing Child and Pediatric Respiratory Infections. Allergie et Immunologie 29(3):73-4; discussion 82, 1997 Mar
- Salam MT, Li YF, Langholz B, Gilliland FD. Early-life environmental risk factors for asthma: findings from the Children’s Health Study. Environ Health Perspect. 2004;112 :760 –765[Web of Science][Medline]
- Nafstad P, Magnus P, Jaakkola JJK. Early respiratory infections and childhood asthma. Pediatrics. 2000;106 (3). Available at: www.pediatrics.org/cgi/content/full/106/3/e38
- Illi S, von Mutius E, Lau S, et al. Early childhood infectious diseases and the development of asthma up to school age: a birth cohort study. BMJ. 2001;322 :390 –395[Abstract/Free Full Text]
- Bodner C, Godden D, Seaton A. Family size, childhood infections and atopic diseases. The Aberdeen WHEASE Group. Thorax. 1998;53 :28 –32[Abstract/Free Full Text]
- Farooqi IS, Hopkin JM. Early childhood infection and atopic disorder. Thorax. 1998;53 :927 –932[Abstract/Free Full Text]
- von Mutius E, Illi S, Hirsch T, Leupold W, Keil U, Weiland SK. Frequency of infections and risk of asthma, atopy and airway hyperresponsiveness in children. Eur Respir J. 1999;14 :4 –11[Abstract]
- Ponsonby AL, Couper D, Dwyer T, Carmichael A, Kemp A. Relationship between early life respiratory illness, family size over time, and the development of asthma and hay fever: a seven year follow-up study. Thorax. 1999;54 :664 –669[Abstract/Free Full Text]
- Williams LK, Peterson EL, Ownby DR, Johnson CC. The relationship between early fever and allergic sensitization at age 6 to 7 years. J Allergy Clin Immunol. 2004;113 :291 –296[CrossRef][Web of Science][Medline]
- McKeever TM, Lewis SA, Smith C, Hubbard R. The importance of prenatal exposures on the development of allergic disease: a birth cohort study using the West Midlands General Practice Database. Am J Respir Crit Care Med. 2002;166 :827 –832[Abstract/Free Full Text]
- Henderson J, Hilliard TN, Sherriff A, Stalker D, Al SN, Thomas HM. Hospitalization for RSV bronchiolitis before 12 months of age and subsequent asthma, atopy and wheeze: a longitudinal birth cohort study. Pediatr Allergy Immunol. 2005;16 :386 –392
- [CrossRef][Web of Science][Medline]
- Bont L, Steijn M, van Aalderen WM, et al. Seasonality of long term wheezing following respiratory syncytial virus lower respiratory tract infection. Thorax. 2004;59 :512 –516[Abstract/Free Full Text]
- Stein RT, Sherrill D, Morgan WJ, et al. Respiratory syncytial virus in early life and risk of wheeze and allergy by age 13 years. Lancet. 1999;354 :541 –545[CrossRef][Web of Science][Medline]
- Sigurs N, Gustafsson PM, Bjarnason R, et al. Severe respiratory syncytial virus bronchiolitis in infancy and asthma and allergy at age 13. Am J Respir Crit Care Med. 2005;171 :137 –141[Abstract/Free Full Text]
- Trefny P, Stricker T, Baerlocher C, Sennhauser FH. Family history of atopy and clinical course of RSV infection in ambulatory and hospitalized infants. Pediatr Pulmonol. 2000;30 :302 –306[CrossRef][Web of Science][Medline]
- Goetghebuer T, Kwiatkowski D, Thomson A, Hull J. Familial susceptibility to severe respiratory infection in early life. Pediatr Pulmonol. 2004;38 :321 –328[CrossRef][Web of Science][Medline]
- Andersen TF, Madsen M, Jorgensen J, Mellemkjoer L, Olsen JH. The Danish National Hospital Register. A valuable source of data for modern health sciences. Dan Med Bull. 1999;46 :263 –268[Web of Science][Medline]
- Stensballe LG, Kristensen K, Nielsen J, Aaby P. Diagnosis coding in The Danish National Patient Registry for respiratory syncytial virus infections. Scand J Inf Dis. 2005;37 :747 –752.[CrossRef][Web of Science][Medline]
- Olsen J, Melbye M, Olsen SF, et al. The Danish National Birth Cohort–its background, structure and aim. Scand J Public Health. 2001;29 :300 –307[CrossRef][Web of Science][Medline]
- Benn CS, Benfeldt E, Andersen PK, Olesen AB, Melbye M, Bjorksten B. Atopic dermatitis in young children: diagnostic criteria for use in epidemiological studies based on telephone interviews. Acta Derm Venereol. 2003;83 :347 –350[CrossRef][Web of Science][Medline]
- Bosken CH, Hunt WC, Lambert WE, Samet JM. A parental history of asthma is a risk factor for wheezing and nonwheezing respiratory illnesses in infants younger than 18 months of age. Am J Respir Crit Care Med. 2000;161 :1810 –1815[Abstract/Free Full Text]
- Murray CS, Pipis SD, McArdle EC, Lowe LA, Custovic A, Woodcock A. Lung function at one month of age as a risk factor for infant respiratory symptoms in a high risk population. Thorax. 2002;57; 388 –392[Abstract/Free Full Text]
- Prescott SL, Macaubas C, Smallacombe T, Holt BJ, Sly PD, Holt PG. Development of allergen-specific T-cell memory in atopic and normal children [see comments]. Lancet. 1999;353 :196 –200[CrossRef][Web of Science][Medline]
- Wang EE, Law BJ, Stephens D. Pediatric Investigators Collaborative Network on Infections in Canada (PICNIC) prospective study of risk factors and outcomes in patients hospitalized with respiratory syncytial viral lower respiratory tract infection. J Pediatr. 1995;126 :212 –219[CrossRef][Web of Science][Medline]
- Groothuis JR, Gutierrez KM, Lauer BA. Respiratory syncytial virus infection in children with bronchopulmonary dysplasia. Pediatrics. 1988;82 :199 –203[Abstract/Free Full Text]
- MacDonald NE, Hall CB, Suffin SC, Alexson C, Harris PJ, Manning JA. Respiratory syncytial viral infection in infants with congenital heart disease. N Engl J Med. 1982;307 :397 –400[Abstract]
- de Sierra TM, Kumar ML, Wasser TE, Murphy BR, Subbarao EK. Respiratory syncytial virus-specific immunoglobulins in preterm infants. J Pediatr. 1993;122 :787 –791[Web of Science][Medline]
- Fixler DE. Respiratory syncytial virus infection in children with congenital heart disease: a review. Pediatr Cardiol. 1996;17 :163 –168[Web of Science][Medline]
- Abman SH, Ogle JW, Butler-Simon N, Rumack CM, Accurso FJ. Role of respiratory syncytial virus in early hospitalizations for respiratory distress of young infants with cystic fibrosis. J Pediatr. 1988;113 :826 –830[CrossRef][Web of Science][Medline]
- Arnold SR, Wang EE, Law BJ, et al. Variable morbidity of respiratory syncytial virus infection in patients with underlying lung disease: a review of the PICNIC RSV database. Pediatric Investigators Collaborative Network on Infections in Canada. Pediatr Infect Dis J. 1999;18 :866 –869[CrossRef][Web of Science][Medline]
- Hall CB, Powell KR, MacDonald NE, et al. Respiratory syncytial viral infection in children with compromised immune function. N Engl J Med. 1986;315 :77 –81[Abstract]
- Nachman SA, Navaie-Waliser M, Qureshi MZ. Rehospitalization with respiratory syncytial virus after neonatal intensive care unit discharge: A 3-year follow-up. Pediatrics. 1997;100(6) . Available at: www.pediatrics.org/cgi/content/full/100/6/e8
- Glezen WP, Paredes A, Allison JE, Taber LH, Frank AL. Risk of respiratory syncytial virus infection for infants from low- income families in relationship to age, sex, ethnic group, and maternal antibody level. J Pediatr. 1981;98 :708 –715[Web of Science][Medline]
- Anderson LJ, Parker RA, Strikas RA, et al. Day-care center attendance and hospitalization for lower respiratory tract illness. Pediatrics. 1988;82 :300 –308[Abstract/Free Full Text]
- Holberg CJ, Wright AL, Martinez FD, Ray CG, Taussig LM, Lebowitz MD. Risk factors for respiratory syncytial virus-associated lower respiratory illnesses in the first year of life. Am J Epidemiol. 1991;133 :1135 –1151[Abstract/Free Full Text]
- Downham MA, Scott R, Sims DG, Webb JK, Gardner PS. Breast-feeding protects against respiratory syncytial virus infections. Br Med J. 1976;2 :274 –276[Abstract/Free Full Text]
- Stensballe LG, Poulsen A, Nante E, et al. Mothers may transmit RSV infection more easily to sons than daughters. Community study from Guinea-Bissau. Scand J Infect Dis. 2004;36 :291 –295[CrossRef][Web of Science][Medline]
- Tepper RS, Morgan WJ, Cota K, Wright A, Taussig LM. Physiologic growth and development of the lung during the first year of life. Am Rev Respir Dis. 1986;134 :513 –519[Web of Science][Medline]
- Martinez FD, Wright AL, Taussig LM, Holberg CJ, Halonen M, Morgan WJ. Asthma and wheezing in the first six years of life. The Group Health Medical Associates. N Engl J Med. 1995;332 :133 –138[Abstract/Free Full Text]
- Landau LI, Morgan W, McCoy KS, Taussig LM. Gender related differences in airway tone in children. Pediatr Pulmonol. 1993;16 :31 –35[Web of Science][Medline]
- Verity CM, Vanheule B, Carswell F, Hughes AO. Bronchial lability and skin reactivity in siblings of asthmatic children. Arch Dis Child. 1984;59 :871 –876[Abstract/Free Full Text]
- Colocho Zelaya EA, Orvell C, Strannegard O. Eosinophil cationic protein in nasopharyngeal secretions and serum of infants infected with respiratory syncytial virus. Pediatr Allergy Immunol. 1994;5 :100 –106[Medline]
- Linneberg A, Petersen J, Gronbaek M, Benn CS. Alcohol during pregnancy and atopic dermatitis in the offspring. Clin Exp Allergy. 2004;34 :1678 –1683[CrossRef][Web of Science][Medline]
- Mok JY, Simpson H. Outcome of acute lower respiratory tract infection in infants: preliminary report of seven-year follow-up study. Br Med J (Clin Res Ed). 1982;285 :333 –337[Medline]
- Noble V, Murray M, Webb MS, Alexander J, Swarbrick AS, Milner AD. Respiratory status and allergy nine to 10 years after acute bronchiolitis. Arch Dis Child. 1997;76 :315 –319[Abstract/Free Full Text]
- Korppi M, Piippo-Savolainen E, Korhonen K, Remes S. Respiratory morbidity 20 years after RSV infection in infancy. Pediatr Pulmonol. 2004;38 :155 –160[CrossRef][Web of Science][Medline]
- Benn CS, Melbye M, Wohlfahrt J, Bjorksten B, Aaby P. Cohort study of sibling effect, infectious diseases, and risk of atopic dermatitis during first 18 months of life. BMJ. 2004;328 :1223[Abstract/Free Full Text]
- Bager P, Westergaard T, Rostgaard K, Hjalgrim H, Melbye M. Age at childhood infections and risk of atopy. Thorax. 2002;57 :379 –382[Abstract/Free Full Text]
- Matricardi PM, Rosmini F, Ferrigno L, et al. Cross sectional retrospective study of prevalence of atopy among Italian military students with antibodies against hepatitis A virus. BMJ. 1997;314 :999 –1003[Abstract/Free Full Text]
- Sly PD, Hibbert ME. Childhood asthma following hospitalization with acute viral bronchiolitis in infancy. Pediatr Pulmonol. 1989;7 :153 –158[Web of Science][Medline]
- Sigurs N, Bjarnason R, Sigurbergsson F, Kjellman M, Björksten B. Asthma and immunoglobulin E antibodies after respiratory syncytial virus bronchiolitis: a prospective cohort study with matched controls. Pediatrics. 1995;95 :500 –505[Abstract/Free Full Text]
- Sigurs N. A cohort of children hospitalised with acute RSV bronchiolitis: impact on later respiratory disease. Paediatr Respir Rev. 2002;3 :177 –183[CrossRef][Medline]
- Stein RT, Sherrill D, Morgan WJ, et al. Respiratory syncytial virus in early life and risk of wheeze and allergy by age 13 years. Lancet. 1999;354 :541 –545[CrossRef][Web of Science][Medline]
- Romagnani S. Human Th1 and Th2 subsets: regulation of differentiation and role in protection and immunopathology. Int Arch Allergy Immunol. 1992;98 :279 –285[Web of Science][Medline]
- Holt PG. Infections and the development of allergy. Toxicol Lett. 1996;86 :205 –210[CrossRef][Web of Science][Medline]
- Beasley R, Pekkanen J, Pearce N. Has the role of atopy in the development of asthma been over-emphasized? Pediatr Pulmonol. 2001;23 :149 –150
- Shaeen SO, Barker DJ, Holgate ST. Do lower respiratory tract infections in early childhood cause chronic obstructive pulmonary disease? Am J Respir Crit Care Med. 1995;151 :1649 –1651[Abstract]
- Nafstad P, Jaakkola JJK, Hagen JA, Botten G, Kongerud J. Breastfeeding, maternal smoking and lower respiratory tract infections. Eur Respir J. 1996;9 :2623 –2629[Abstract]
- Nafstad P, Kongerud J, Botten G, Hagen JA, Jaakkola JJK. The role of passive smoking in the development of bronchial obstruction the first 2 years of life. Epidemiology. 1997;8 :293 –297[CrossRef][Web of Science][Medline]
- ISAAC Steering Committee. Phase II Modules of The International Study of Asthma and Allergies in Childhood (ISAAC). Münster, Germany: Institute of Epidemiology and Social Medicine; 1998
- Meinert R, Frischer T, Karmaus W, Kuehr J. Influence of skin prick test criteria on estimation of prevalence and incidence of allergic sensitization in children. Allergy. 1994;49 :526 –532[Web of Science][Medline]
- Martinez FD, Wright AL, Taussig LM, Holberg CJ, Harlonen M, Morgan WJ. Asthma and wheezing the first six years of life. N Engl J Med. 1995;332 :133 –138[Abstract/Free Full Text]
- Ogra PL. Respiratory syncytial virus: the virus, the disease and the immune response. Paediatr Respir Rev. 2004;5(suppl A) :S119 –S126
- Van Bever HP, Wieringa MH, Weyler JJ, Nelen VJ, Fortuin M, Vermeire PA. Croup and recurrent croup: their association with asthma and allergy. An epidemiological study on 5–8-year-old children. Eur J Pediatr. 1999;158 :253 –257[CrossRef][Web of Science][Medline]
- Castro-Rodriguez JA, Holberg CJ, Morgan WJ, et al. Relation of two different subtypes of croup before age three to wheezing, atopy, and pulmonary function during childhood: a prospective study. Pediatrics. 2001;107 :512 –518[Abstract/Free Full Text]
- Nystad, W, Skrondal A, Magnus P. Recurrent respiratory tract infections during the first 3 years of life and atopy at school age. Allergy. 1998;53 :1189 –1194[Web of Science][Medline]
- Nja F, Nystad W, Hetlevik O, Carlsen KCL, Carlsen KH. Airway infections in infancy and the presence of allergy and asthma in school age children. Arch Dis Child. 2003;88 :566 –569[Abstract/Free Full Text]
- American Academy of Family Physicians; American Academy of Otolaryngology Head and Neck Surgery; American Academy of Pediatrics Subcommittee on Otitis Media With Effusion. Otitis media with effusion. Pediatrics. 2004;113 :1412 –1429[Abstract/Free Full Text]
- Doyle WJ. The link between allergic rhinitis and otitis media. Curr Opin Allergy Clin Immunol. 2002;2 :21 –25[CrossRef][Medline]
Supported byWidodo judarwanto, pediatrician
Children’s Allergy Center Online Picky Eaters Clinic, Klinik Kesulitan makan Pada Anak
Information on this web site is provided for informational purposes only and is not a substitute for professional medical advice. You should not use the information on this web site for diagnosing or treating a medical or health condition. You should carefully read all product packaging. If you have or suspect you have a medical problem, promptly contact your professional healthcare provider.
Copyright © 2010, Children Allergy Center Information Education Network. All rights reserved