Background Many young children wheeze during viral respiratoryinfections, but the pathogenesis of these episodes and theirrelation to the development of asthma later in life are notwell understood.
Methods In a prospective study, we investigated the factorsaffecting wheezing before the age of three years and their relationto wheezing at six years of age. Of 1246 newborns in the Tucson,Arizona, area enrolled between May 1980 and October 1984, follow-updata at both three and six years of age were available for 826.For these children, assessments in infancy included measurementof cord-serum IgE levels (measured in 750 children), pulmonary-functiontesting before any lower respiratory tract illness had occurred(125), measurement of serum IgE levels at nine months of age(672), and questionnaires completed by the children's parentswhen the children were one year old (800). Assessments at sixyears of age included measurement of serum IgE levels (in 460),pulmonary-function testing (526), and skin allergy testing (629).
Results At the age of six years, 425 children (51.5 percent)had never wheezed, 164 (19.9 percent) had had at least one lowerrespiratory tract illness with wheezing during the first threeyears of life but had no wheezing at six years of age, 124 (15.0percent) had no wheezing before the age of three years but hadwheezing at the age of six years, and 113 (13.7 percent) hadwheezing both before three years of age and at six years ofage. The children who had wheezing before three years of agebut not at the age of six had diminished airway function (length-adjustedmaximal expiratory flow at functional residual capacity [VsubmaxFRC]) both before the age of one year and at the age of sixyears, were more likely than the other children to have motherswho smoked but not mothers with asthma, and did not have elevatedserum IgE levels or skin-test reactivity. Children who startedwheezing in early life and continued to wheeze at the age ofsix were more likely than the children who never wheezed tohave mothers with a history of asthma (P<0.001), to haveelevated serum IgE levels (P<0.01) and normal lung functionin the first year of life, and to have elevated serum IgE levels(P<0.001) and diminished values for VmaxFRC (P<0.01) atsix years of age.
Conclusions The majority of infants with wheezing have transientconditions associated with diminished airway function at birthand do not have increased risks of asthma or allergies laterin life. In a substantial minority of infants, however, wheezingepisodes are probably related to a predisposition to asthma.
Although asthma may originate soon after birth,1 the naturalhistory of the disease is poorly understood. Many infants haveepisodes of wheezing associated with viral respiratory illnesses.2Neither the pathogenesis of these episodes nor their relationto asthma has been completely elucidated.3 In older childrenand adults, the prevalence of asthma is strongly correlatedwith serum IgE levels and with skin-test reactivity to allergens,4,5but in one study no such relation was evident between earlywheezing and serum IgE levels at birth.6 Infants who have respiratoryillnesses with wheezing in the first year of life have lowerlevels of lung function before any lower respiratory illnessdevelops than do infants who do not have illnesses with wheezing.7This finding suggests that small airways predispose many infantsto wheezing in association with common viral infections. However,it is possible that acute bronchial obstruction may have a varietyof causes in early life, and a minority of infants with asthmamay coexist with a larger group of infants with wheezing whohave a more benign condition that is not mediated by IgE.
Older children with asthma have lower levels of lung functionthan children without asthma.8 It is not known whether the reductionsin lung function present before asthma develops contribute toasthma and continue to be present later in life or whether reducedlung function in children with asthma is the consequence ofchronic airway inflammation.
We studied the natural history of wheezing in the first sixyears of life. Specifically, we assessed the factors that affectwheezing before the age of three years and their relation towheezing at six years of age.
Methods
The children we studied were enrolled as newborns between May1980 and October 1984 in the Tucson Children's Respiratory Study.9Their parents were patients of Group Health Medical Associates,a large health maintenance organization in Tucson, Arizona,and were contacted shortly after their children were born. Informedconsent was obtained from the parents of 1246 newborns.
At the time of enrollment, the parents completed a questionnaireabout their history of respiratory illness, smoking habits,and education. They were instructed to take their children tothe pediatrician whenever the children had any of a definedset of signs and symptoms of lower respiratory tract illness(deep or ``wet'' chest cough, wheezing, hoarseness, stridor,or shortness of breath). The pediatricians obtained a detailedhistory at the time of such illnesses and recorded all relevantsigns and symptoms (including wheezing on auscultation). Figure 1shows the number of children for whom complete follow-up informationon lower respiratory tract illnesses and complete data fromquestionnaires and tests were available.
Figure 1. Number of Subjects Enrolled, Number with Complete Follow-up for Lower Respiratory Tract Illnesses in the First Three Years of Life, and Number for Whom Complete Data Were Available from Questionnaires and Tests. A total of 826 children had follow-up data at three and six years of age and were included in the study.
Parents completed a questionnaire during their child's secondyear of life (mean[ ±SD] age, 1.6 ±0.4 years).Among other questions, parents were asked whether the child's``chest had ever sounded wheezy or whistling apart from colds''and how frequently the child wheezed. Parents were also askedwhether their child ever had a runny nose apart from colds andwhether a doctor had ever given the child a diagnosis of eczema.When the children reached a mean age of 6.3 ±0.9 years,parents again answered a questionnaire about the child's respiratoryillnesses (referred to as the 6-year survey). In that questionnaire,current wheezing was defined as at least one episode of wheezingduring the previous year.
During the first year of life, 176 infants underwent pulmonary-functiontesting. A detailed description of the selection criteria andthe medical and social characteristics of these infants, ascompared with those who were not tested, was reported earlier7;the frequency of a family history of asthma or allergies didnot differ significantly between the infants who underwent pulmonary-functiontesting and those who were not tested. Of the 176 infants initiallytested, 125 were tested before any lower respiratory tract illnessoccurred; complete follow-up data to the age of six years wereavailable for these infants. Their mean age at the time of testingwas 2.4 ±2.0 months.
Partial expiratory flow-volume curves were obtained by the chest-compressiontechnique.10 Briefly, informed consent was obtained from theparents, and the children were usually sedated with chloralhydrate (50 to 60 mg per kilogram of body weight). A plasticbag connected to a pressure reservoir was tightly wrapped aroundthe child's chest and abdomen. A mask connected to a pneumotachygraphwas sealed around the child's mouth and nose, and tidal flow-volumeloops were displayed on a monitor. At end-tidal inspiration,the bag was rapidly inflated to a known pressure, compressingthe child's chest and forcing air out of the lungs. The flowat the end-tidal expiration point was recorded from the forcedflow-volume loops. This maneuver was repeated with incrementsin pressure of 5 to 10 cm of water. The maximal pressure appliedto the thorax was the pressure at which no further increasein flow was obtained; this value -- the maximal expiratory flowat functional residual capacity (Vsub maxFRC, expressed in millilitersper second) -- was recorded and used in the analysis. Vsub maxFRCis believed to reflect the size of the intrapulmonary airways.11
At the time of the six-year survey, partial expiratory flow-volumecurves were obtained with maneuvers to measure voluntary maximalexpiratory flow.12 Tidal flow-volume loops were recorded ona computer screen as described above. As the child approachedend-tidal inspiration, he or she was encouraged to expel airforcefully, and a partial flow-volume curve was obtained. VsubmaxFRC was calculated from at least three acceptable expirations;the highest value obtained was used in our analyses.
Total serum IgE levels were measured with the paper radioimmunosorbenttest (Pharmacia Diagnostics, Piscataway, N.J.) in samples obtainedfrom cord blood, from blood obtained at a median age of 9.3months (referred to as the 9-month sample), and from blood obtainedat the time of the 6-year survey.
Skin allergy tests were performed concomitantly with lung-functiontesting at the time of the six-year survey with extracts ofseven common aeroallergens in the Tucson area (Hollister-StierLaboratories, Everett, Wash.). A child was considered to haveatopy if he or she had at least one positive skin-test reaction(>2 mm of induration) to an aeroallergen. The aeroallergenstested were house-dust mix, alternaria, Bermuda grass, carelessweed, mesquite, mulberry, and olive.
Statistical Analysis
Total serum IgE levels were expressed in international unitsper milliliter (1 IU per milliliter corresponded to 2.4 microgper liter). Log IgE values were adjusted for age according tostandard regression techniques and expressed in terms of themedian age (9.3 months) of the sample.
Values for Vsub maxFRC were logarithmically transformed forboth age groups and adjusted for length or height. Results werestandardized to the children's average length (57.4 cm) beforethe age of one year or height (110.3 cm) at the age of six.
Analysis of variance, Duncan's multiple-comparison test, chi-squaretests, and logistic regression were used to compare means andproportions.13 The 95 percent confidence intervals for oddsratios were calculated with standard algorithms.14 Statisticalsignificance was defined by a two-sided alpha level of 0.05.
This research was approved by the Human Subjects Committee atthe University of Arizona. The parents signed separate consentforms for the infants' initial enrollment and for the otherstudies described in this report.
Results
When the 826 children included in this study were compared withthe 420 who were excluded because of incomplete data, the frequencyof a family history of asthma and the distribution of ethnicbackgrounds were similar. However, the children with completedata tended to belong to families with a higher socioeconomicstatus and a lower prevalence of maternal smoking (data notshown).
Children were assigned to four categories according to theirhistory of wheezing: those who had no recorded lower respiratorytract illness with wheezing during the first three years oflife and had no wheezing at six years of age (children who hadnever had wheezing); those with at least one lower respiratorytract illness with wheezing during the first three years oflife but no wheezing at six years of age (those with transientearly wheezing); those who had no lower respiratory tract illnesswith wheezing during the first three years of life but who hadwheezing at six years of age (those with wheezing of late onset);and those who had at least one lower respiratory tract illnesswith wheezing in the first three years of life and had wheezingat six years of age (those with persistent wheezing). A totalof 425 children (51.5 percent) were classified as never havingwheezed, 164 (19.9 percent) as having had transient early wheezing,124 (15.0 percent) as having wheezing of late onset, and 113(13.7 percent) as having persistent wheezing.
Of 277 children who had wheezing before the age of three, 164(59.2 percent) had not wheezed during the previous year whenthey were evaluated at six years of age. Maternal asthma, maternalsmoking, rhinitis apart from colds, eczema during the firstyear of life, male sex, and Hispanic ethnic background wereall independently associated with persistent wheezing. Of thevariables we considered, only maternal smoking was significantlyassociated with transient early wheezing (Table 1). Childrenwith wheezing of late onset were significantly more likely thanthose who had never wheezed to have mothers with asthma, tobe male, and to have had rhinitis in the first year of life.Those with persistent wheezing were significantly more likelythan those without wheezing to have mothers with asthma (P<0.001).The results in each category of wheezing were not changed byadjustment for the parents' level of education.
Table 1. Adjusted Odds Ratios for Transient Early Wheezing, Late-Onset Wheezing, and Persistent Wheezing, According to Risk Factors Present at One Year of Age, and Prevalence of Risk Factors.
When compared with the children with transient early wheezing,those with persistent wheezing were more than twice as likelyto have wheezed often or very often (odds ratio, 2.3; 95 percentconfidence interval, 1.4 to 3.8; P = 0.001) and were more likelyto have had wheezing without colds during infancy (odds ratio,1.8; 95 percent confidence interval, 1.0 to 3.4; P = 0.05).At six years of age, 22.5 percent of children with late-onsetwheezing had been given a diagnosis of asthma, as compared with46.0 percent of children with persistent wheezing (P<0.001);25.0 percent of children with late-onset wheezing had been givena diagnosis of bronchitis without asthma, as had 22.1 percentof those with persistent wheezing (P = 0.7).
Children with transient early wheezing had significantly lowerlength-adjusted values for Vsub maxFRC in infancy than all theother groups (Table 2). The children with persistent wheezingor wheezing of late onset had Vsub maxFRC values that were notsignificantly different from those of the children who had neverhad wheezing. At the age of six, the children with transientearly wheezing still had significantly lower height-adjustedVsub maxFRC values than those who had never wheezed, and thechildren with persistent wheezing had the lowest levels of lungfunction of all the groups. As compared with the children whohad never wheezed, those with persistent wheezing were significantlymore likely to have diminished values for Vsub maxFRC (P<0.01).Children with late-onset wheezing had Vsub maxFRC levels thatwere not significantly different from those of the childrenwho had never wheezed.
Table 2. Maximal Expiratory Flow at Functional Residual Capacity (Vsub maxFRC) during the First Year of Life and at Six Years of Age, According to History of Wheezing.
Cord-serum IgE levels were unrelated to a later history of wheezing(Figure 2). Only children with persistent wheezing had significantlyhigher IgE levels at nine months of age than those who had neverwheezed (P<0.01). The geometric mean IgE levels were 3.4IU per milliliter (95 percent confidence interval, 3.0 to 3.9)for children who had never wheezed, 3.7 (95 percent confidenceinterval, 3.1 to 4.4) for those with transient early wheezing,3.8 (95 percent confidence interval, 2.9 to 5.0) for those withwheezing of late onset, and 5.2 (95 percent confidence interval,3.8 to 7.2) for those with persistent wheezing. The risk ofbelonging to any of the three groups with wheezing was evaluatedaccording to the level of IgE at nine months of age (Figure 2).A direct relation between IgE levels and wheezing was seenonly for children with persistent wheezing (P = 0.02).
Figure 2. Proportion of Subjects Who Had Transient Early Wheezing, Wheezing of Late Onset, and Persistent Wheezing, According to Cord-Serum IgE Levels and Serum IgE Levels at Nine Months of Age. The categories of wheezing are defined in the text. The numbers of children with the various IgE levels were as follows: for cord serum, not detectable (ND), 290;<0.1 IU per milliliter, 296; 0.1 to 0.2 IU per milliliter, 117; 0.3 to 0.9 IU per milliliter, 20; and greater/equal 1.0 IU per milliliter, 10; for serum at nine months,<1.0 IU per milliliter, 83; 1.0 to 3.1 IU per milliliter, 230; 3.2 to 9.9 IU per milliliter, 209; 10.0 to 31.9 IU per milliliter, 123; and greater/equal 32.0 IU per milliliter, 27. P values for trend within the groups were determined by the chi-square test.
Children with transient early wheezing and those who had neverwheezed had similar serum IgE levels and a similar prevalenceof atopy at the age of six years (Table 3). Those with persistentwheezing had significantly higher levels of IgE than those whohad never wheezed (P<0.01). Children with late-onset wheezingdid not have significantly elevated serum IgE levels as comparedwith those who had never wheezed. Atopy was significantly moreprevalent in both groups of children with wheezing at the ageof six than in the group that had never wheezed. After adjustmentfor skin-test reactivity with multiple regression analysis,the children with persistent wheezing had significantly higherlevels of IgE at the age of six years than the children withlate-onset wheezing (P = 0.03).
Table 3. Total Serum IgE Levels and Prevalence of Positive Skin Tests for Reactivity to Aeroallergens in Children Six Years Old, According to History of Wheezing.
Discussion
We found that wheezing in the first three years of life hada rather benign prognosis. Although one third of all childrenthree years of age or younger had lower respiratory tract illnesseswith wheezing, almost 60 percent of these children had stoppedwheezing by the age of six years. Children with transient earlywheezing were distinguished from the other groups who had wheezingby their lower levels of lung function, as indicated by theirvalues for Vsub maxFRC. As described earlier,15 this diminishedlung function was evident shortly after birth and before anylower respiratory tract illness had occurred. One possibilityis that this finding reflected congenitally smaller airwaysand predisposed these infants to wheezing in early life. Wefound that children with transient early wheezing still hadreduced values for Vsub maxFRC at six years of age, as comparedwith their peers, although the children were no longer symptomatic.As their airways grow in absolute size with age, these childrenmay become less apt to have wheezing during viral infections.
Smoking by a child's mother was also a risk factor for transientearly wheezing. The infants of mothers who smoked during pregnancyhad significantly lower values for Vsub maxFRC16 than the infantsof mothers who did not smoke. The association between maternalsmoking and transient early wheezing may be mediated, at leastin part, by smaller airways in the children of women who smoke.
Children with persistent wheezing had initial values for VsubmaxFRC that were similar to those of the children who neverwheezed but were almost 50 percent higher than those of childrenwith transient early wheezing. Factors other than small airwaysmay cause early wheezing in infants in whom episodes of wheezingpersist up to the age of six years. Children with persistentwheezing had more frequent symptoms during the first year oflife than those with transient early wheezing. Most of the riskfactors for persistent wheezing (eczema, rhinitis apart fromcolds, and maternal asthma, among others) were not associatedwith increased risk among the children with transient earlywheezing. Maternal smoking was the only risk factor common toboth groups, suggesting that exposure to tobacco smoke may haveeffects other than those on airway growth in utero.17
There was a significant, direct relation between the risk ofpersistent wheezing and the serum IgE level at nine months ofage. This relation was very similar to that reported betweenserum IgE levels and asthma in older children and adults,4,5and it contrasts with the lack of association between transientearly wheezing or late-onset wheezing and serum IgE levels atnine months. No relation was found between the risk of persistentwheezing at six years of age and cord-serum IgE levels, suggestingthat some form of IgE-mediated sensitization may occur duringthe first year of life in children with persistent wheezing.Such sensitization may contribute to early wheezing, in muchthe same way as it is thought to predispose older children toasthma.
We could not determine the nature of this allergic sensitizationon the basis of our data. It is clear, however, that by theage of six years, children with persistent wheezing were asfrequently sensitized to common aeroallergens as those withwheezing of late onset. One hypothesis is that children withpersistent wheezing may have been sensitized to these antigensduring the first year of life, whereas children with late-onsetwheezing were not. An alternative hypothesis is that childrenwith persistent wheezing are predisposed to produce large quantitiesof IgE in response to a variety of antigens and that this enhancedIgE reactivity may be expressed in response to different allergensat different ages. Further studies of allergic sensitizationin early life are indicated.18
Most of the children with lower respiratory tract illnessesin our study were infected with respiratory syncytial virusor parainfluenza viruses.2 Welliver et al. found a higher prevalenceof specific IgE against respiratory syncytial virus19 and parainfluenzavirus20 in the nasal secretions of infants with wheezing whohad these infections than in the secretions of infants withthese infections who did not have wheezing. In infants withconfirmed respiratory syncytial virus infections in the firstsix months of life, the frequency of persistent wheezing upto seven or eight years of age was directly related to the levelof respiratory syncytial virus-specific IgE in their nasopharyngealsecretions during the initial episode.21 The children who hadpersistent wheezing in our study may have been more prone thanthe others to produce virus-specific IgE in early life. Thisfactor could explain their higher levels of IgE at a mean ageof nine months.
Children with persistent wheezing had significantly reducedlung function, as indicated by Vsub maxFRC values, at the ageof six years. This deterioration in airway function is consistentwith the substantial deficits in lung function reported in olderchildren with asthma.8 Our data suggest that among childrenwith persistent wheezing these deficits are not caused by poorerinitial lung function but, rather, may reflect the effects ofthe chronic disease process on the bronchi. We do not know whetherthe deficits reflect irreversible damage to the airways or areversible increase in airway muscle tone. Recent reports suggest,however, that in people with asthma, lung volume and maximalflow grow at similar, normal rates from 9 to 17 years of ageand that any irreversible damage may have already occurred by9 years of age.22
Our data did not permit us to elucidate the mechanisms of thedeficits in lung function in children with persistent wheezing.We doubt, however, that they result from direct, nonspecificinjuries produced by viral infections in early life. If thiswere the case, similar deficits should have been seen amongthe children with transient early wheezing. It is possible thatin children with persistent wheezing, much as in older patientswith asthma, chronically elevated serum IgE levels may be associatedwith chronic airway inflammation,23 persistent bronchial hyperresponsiveness,5and abnormalities in the development of airway function.24 Suchassociations could also help to explain why children with late-onsetwheezing, whose serum IgE levels were not elevated at nine monthsof age and were only mildly elevated at six years, had lungfunction at the age of six that was within the normal range.
In summary, our findings suggest that most infants who wheezehave transient conditions associated with diminished airwayfunction and have no increased risk of asthma or allergies laterin life. In a minority of infants, early wheezing episodes areprobably related to a predisposition to asthma. Such childrenalready have elevated serum IgE levels during the first monthsof life and have substantial deficits in lung function by theage of six years.
Supported by a Specialized Center of Research Grant (HL14136)from the National Institutes of Health.
We are indebted to Benjamin Burrows, M.D., for his advice; toMarilyn Smith, R.N., and Lydia De La Ossa, R.N., the study nurses;to Shelley Radford and Bruce Saul for technical assistance;and to Maureen Cameron for assistance in the preparation ofthe manuscript.
Source Information
From the Respiratory Sciences Center (F.D.M., A.L.W., L.M.T., C.J.H., M.H., W.J.M.) and the Department of Pediatrics (F.D.M., A.L.W., L.M.T., W.J.M.), University of Arizona College of Medicine, Tucson.
The members of the Group Health Medical Associates were John Bean, M.D., Henry Bianchi, M.D., John Curtiss, M.D., John Ey, M.D., Alejandro Sanguineti, M.D., Barbara Smith, M.D., Terry Vondrak, M.D., Neil West, M.D., and Maureen McLellan, R.N., P.N.P.
Address reprint requests to Dr. Martinez at the Respiratory Sciences Center, Arizona Health Sciences Center, 1501 N. Campbell Ave., Tucson, AZ 85724.
References
Martinez FD. The origins of asthma in early life. In: Postma DS, Gerritsen J, eds. Proceedings of the Bronchitis V International Symposium, Groningen, the Netherlands. Assen, the Netherlands: Van Gorcum, 1994:161-9.
Wright AL, Taussig LM, Ray CG, Harrison HR, Holberg CJ. The Tucson Children's Respiratory Study. II. Lower respiratory tract illness in the first year of life. Am J Epidemiol 1989;129:1232-1246. [Free Full Text]
Samet JM, Tager IB, Speizer FE. The relationship between respiratory illness in childhood and chronic air-flow obstruction in adulthood. Am Rev Respir Dis 1983;127:508-523. [Medline]
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;320:271-277. [Abstract]
Sears MR, Burrows B, Flannery EM, Herbison GP, Hewitt CJ, Holdaway MD. Relation between airway responsiveness and serum IgE in children with asthma and in apparently normal children. N Engl J Med 1991;325:1067-1071. [Abstract]
Halonen M, Stern D, Taussig LM, Wright AL, Ray CG, Martinez FD. The predictive relationship between serum IgE levels at birth and subsequent incidences of lower respiratory illnesses and eczema in infants. Am Rev Respir Dis 1992;146:866-870. [Medline]
Martinez FD, Morgan WJ, Wright AL, Holberg CJ, Taussig LM, GHMA Personnel. Diminished lung function as a predisposing factor for wheezing respiratory illness in infants. N Engl J Med 1988;319:1112-1117. [Abstract]
Weiss ST, Tosteson TD, Segal MR, Tager IB, Redline S, Speizer FE. Effects of asthma on pulmonary function in children: a longitudinal population-based study. Am Rev Respir Dis 1992;145:58-64. [Medline]
Taussig LM, Wright AL, Morgan WJ, Harrison HR, Ray CG, Group Health Medical Associates. The Tucson Children's Respiratory Study. I. Design and implementation of a prospective study of acute and chronic respiratory illness in children. Am J Epidemiol 1989;129:1219-1231. [Free Full Text]
Tepper RS, Morgan WJ, Cota K, Wright AL, Taussig LM, GHMA Pediatricians. Physiologic growth and development of the lung during the first year of life. Am Rev Respir Dis 1986;134:513-519. [Erratum, Rev Respir Dis 1987;136:800.] [Medline]
NHLBI workshop summary: assessment of lung function and dysfunction in studies of infants and children. Am Rev Respir Dis 1993;148:1105-1108. [Medline]
Taussig LM. Maximal expiratory flows at functional residual capacity: a test of lung function for young children. Am Rev Respir Dis 1977;116:1031-1038. [Medline]
Armitage P, Berry G. Statistical methods in medical research. 2nd ed. Oxford, England: Blackwell Scientific, 1987.
Woolf B. On estimating the relation between blood group and disease. Ann Hum Genet 1954;19:251-253. [CrossRef]
Martinez FD, Morgan WJ, Wright AL, Holberg CJ, Taussig LM. Initial airway function is a risk factor for recurrent wheezing respiratory illnesses during the first three years of life. Am Rev Respir Dis 1991;143:312-316. [Medline]
Tager IB, Hanrahan JP, Tosteson TD, et al. Lung function, pre- and post-natal smoke exposure, and wheezing in the first year of life. Am Rev Respir Dis 1993;147:811-817. [Medline]
Martinez FD, Antognoni G, Macri F, et al. Parental smoking enhances bronchial responsiveness in nine-year-old children. Am Rev Respir Dis 1988;138:518-523. [Medline]
Rowntree S, Cogswell JJ, Platts-Mills TAE, Mitchell EB. Development of IgE and IgG antibodies to food and inhalant allergens in children at risk of allergic disease. Arch Dis Child 1985;60:727-735. [Free Full Text]
Welliver RC, Wong DT, Sun M, Middleton E Jr, Vaughan RS, Ogra PL. The development of respiratory syncytial virus-specific IgE and the release of histamine in nasopharyngeal secretions after infection. N Engl J Med 1981;305:841-846. [Abstract]
Welliver RC, Wong DT, Middleton E Jr, Sun M, McCarthy N, Ogra PL. Role of parainfluenza virus-specific IgE in pathogenesis of croup and wheezing subsequent to infection. J Pediatr 1982;101:889-896. [CrossRef][Medline]
Welliver RC, Duffy L. The relationship of RSV-specific immunoglobulin E antibody responses in infancy, recurrent wheezing, and pulmonary function at age 7-8 years. Pediatr Pulmonol 1993;15:19-27. [Medline]
Merkus PJFM, van Essen-Zandvliet EEM, Kouwenberg JM, et al. Large lungs after childhood asthma: a case-control study. Am Rev Respir Dis 1993;148:1484-1489. [Medline]
Pattemore PK, Holgate ST. Bronchial hyperresponsiveness and its relationship to asthma in childhood. Clin Exp Allergy 1993;23:886-900. [CrossRef][Medline]
Redline S, Tager IB, Segal MR, Gold D, Speizer FE, Weiss ST. The relationship between longitudinal change in pulmonary function and nonspecific airway responsiveness in children and young adults. Am Rev Respir Dis 1989;140:179-184. [Medline]
To, T., Wang, C., Guan, J., McLimont, S., Gershon, A. S.
(2010). What Is the Lifetime Risk of Physician-diagnosed Asthma in Ontario, Canada?. Am. J. Respir. Crit. Care Med.
181: 337-343
[Abstract][Full Text]
Sharma, S., Tantisira, K., Carey, V., Murphy, A. J., Lasky-Su, J., Celedon, J. C., Lazarus, R., Klanderman, B., Rogers, A., Soto-Quiros, M., Avila, L., Mariani, T., Gaedigk, R., Leeder, S., Torday, J., Warburton, D., Raby, B., Weiss, S. T.
(2010). A Role for Wnt Signaling Genes in the Pathogenesis of Impaired Lung Function in Asthma. Am. J. Respir. Crit. Care Med.
181: 328-336
[Abstract][Full Text]
Lombardi, V., Stock, P., Singh, A. K., Kerzerho, J., Yang, W., Sullivan, B. A., Li, X., Shiratsuchi, T., Hnatiuk, N. E., Howell, A. R., Yu, K. O. A., Porcelli, S. A., Tsuji, M., Kronenberg, M., Wilson, S. B., Akbari, O.
(2010). A CD1d-Dependent Antagonist Inhibits the Activation of Invariant NKT Cells and Prevents Development of Allergen-Induced Airway Hyperreactivity. J. Immunol.
184: 2107-2115
[Abstract][Full Text]
Leung, T. F., To, M. Y., Yeung, A. C. M., Wong, Y. S., Wong, G. W. K., Chan, P. K. S.
(2010). Multiplex Molecular Detection of Respiratory Pathogens in Children With Asthma Exacerbation. Chest
137: 348-354
[Abstract][Full Text]
Sleiman, P. M.A., Flory, J., Imielinski, M., Bradfield, J. P., Annaiah, K., Willis-Owen, S. A.G., Wang, K., Rafaels, N. M., Michel, S., Bonnelykke, K., Zhang, H., Kim, C. E., Frackelton, E. C., Glessner, J. T., Hou, C., Otieno, F. G., Santa, E., Thomas, K., Smith, R. M., Glaberson, W. R., Garris, M., Chiavacci, R. M., Beaty, T. H., Ruczinski, I., Orange, J. M., Allen, J., Spergel, J. M., Grundmeier, R., Mathias, R. A., Christie, J. D., von Mutius, E., Cookson, W. O.C., Kabesch, M., Moffatt, M. F., Grunstein, M. M., Barnes, K. C., Devoto, M., Magnusson, M., Li, H., Grant, S. F.A., Bisgaard, H., Hakonarson, H.
(2010). Variants of DENND1B Associated with Asthma in Children. NEJM
362: 36-44
[Abstract][Full Text]
Hylkema, M. N., Blacquiere, M. J.
(2009). Intrauterine Effects of Maternal Smoking on Sensitization, Asthma, and Chronic Obstructive Pulmonary Disease. Proc Am Thorac Soc
6: 660-662
[Abstract][Full Text]
Subbarao, P., Mandhane, P. J., Sears, M. R.
(2009). Asthma: epidemiology, etiology and risk factors. CMAJ
181: E181-E190
[Full Text]
El-Zein, M., Parent, M.-E., Benedetti, A., Rousseau, M.-C.
(2009). Does BCG vaccination protect against the development of childhood asthma? A systematic review and meta-analysis of epidemiological studies. Int J Epidemiol
0: dyp307v1-dyp307
[Abstract][Full Text]
Renouf, P.
(2009). Review: inhaled corticosteroids reduce wheezing and asthma exacerbations in infants and preschool children. Evid. Based Nurs.
12: 105-105
[Full Text]
Saglani, S., Mathie, S. A., Gregory, L. G., Bell, M. J., Bush, A., Lloyd, C. M.
(2009). Pathophysiological Features of Asthma Develop in Parallel in House Dust Mite-Exposed Neonatal Mice. Am. J. Respir. Cell Mol. Bio.
41: 281-289
[Abstract][Full Text]
Sahib El-Radhi, A., Patel, S.
(2009). The Clinical Course of Childhood Asthma in Association with Fever. CLIN PEDIATR
48: 627-631
[Abstract]
Pelkonen, A S, Malmstrom, K, Malmberg, L P, Sarna, S, Turpeinen, M, Kajosaari, M, Haahtela, T, Makela, M J
(2009). Budesonide improves decreased airway conductance in infants with respiratory symptoms. Arch. Dis. Child.
94: 536-541
[Abstract][Full Text]
Finn, P. W., Bigby, T. D.
(2009). Innate Immunity and Asthma. Proc Am Thorac Soc
6: 260-265
[Abstract][Full Text]
Gelfand, E. W.
(2009). Pediatric Asthma: A Different Disease. Proc Am Thorac Soc
6: 278-282
[Abstract][Full Text]
Lemanske, R. F. Jr.
(2009). Asthma Therapies Revisited: What Have We Learned?. Proc Am Thorac Soc
6: 312-315
[Abstract][Full Text]
Henderson, J, Granell, R, Sterne, J
(2009). The search for new asthma phenotypes. Arch. Dis. Child.
94: 333-336
[Full Text]
Bush, A.
(2009). Update in Pediatric Lung Disease 2008. Am. J. Respir. Crit. Care Med.
179: 637-649
[Full Text]
Bush, A., Brand, P. L. P.
(2009). From the authors. Eur Respir J
33: 945-945
[Full Text]
Bollag, U., Grize, L., Braun-Fahrlander, C.
(2009). Is the ebb of asthma due to the decline of allergic asthma? A prospective consultation-based study by the Swiss Sentinel Surveillance Network, 1999-2005. Fam Pract
26: 96-101
[Abstract][Full Text]
Harley, K G, Macher, J M, Lipsett, M, Duramad, P, Holland, N T, Prager, S S, Ferber, J, Bradman, A, Eskenazi, B, Tager, I B
(2009). Fungi and pollen exposure in the first months of life and risk of early childhood wheezing. Thorax
64: 353-358
[Abstract][Full Text]
Spycher, B. D., Silverman, M., Egger, M., Zwahlen, M., Kuehni, C. E.
(2009). Routine Vaccination Against Pertussis and the Risk of Childhood Asthma: A Population-Based Cohort Study. Pediatrics
123: 944-950
[Abstract][Full Text]
Castro-Rodriguez, J. A., Rodrigo, G. J.
(2009). Efficacy of Inhaled Corticosteroids in Infants and Preschoolers With Recurrent Wheezing and Asthma: A Systematic Review With Meta-analysis. Pediatrics
123: e519-e525
[Abstract][Full Text]
Borrego, L M, Stocks, J, Leiria-Pinto, P, Peralta, I, Romeira, A M, Neuparth, N, Rosado-Pinto, J E, Hoo, A-F
(2009). Lung function and clinical risk factors for asthma in infants and young children with recurrent wheeze. Thorax
64: 203-209
[Abstract][Full Text]
Haberg, S E, London, S J, Stigum, H, Nafstad, P, Nystad, W
(2009). Folic acid supplements in pregnancy and early childhood respiratory health. Arch. Dis. Child.
94: 180-184
[Abstract][Full Text]
Bisgaard, H., Bonnelykke, K., Sleiman, P. M. A., Brasholt, M., Chawes, B., Kreiner-Moller, E., Stage, M., Kim, C., Tavendale, R., Baty, F., Pipper, C. B., Palmer, C. N. A., Hakonarsson, H.
(2009). Chromosome 17q21 Gene Variants Are Associated with Asthma and Exacerbations but Not Atopy in Early Childhood. Am. J. Respir. Crit. Care Med.
179: 179-185
[Abstract][Full Text]
Roduit, C, Scholtens, S, de Jongste, J C, Wijga, A H, Gerritsen, J, Postma, D S, Brunekreef, B, Hoekstra, M O, Aalberse, R, Smit, H A
(2009). Asthma at 8 years of age in children born by caesarean section. Thorax
64: 107-113
[Abstract][Full Text]
Panickar, J., Lakhanpaul, M., Lambert, P. C., Kenia, P., Stephenson, T., Smyth, A., Grigg, J.
(2009). Oral Prednisolone for Preschool Children with Acute Virus-Induced Wheezing. NEJM
360: 329-338
[Abstract][Full Text]
Ducharme, F. M., Lemire, C., Noya, F. J.D., Davis, G. M., Alos, N., Leblond, H., Savdie, C., Collet, J.-P., Khomenko, L., Rivard, G., Platt, R. W.
(2009). Preemptive Use of High-Dose Fluticasone for Virus-Induced Wheezing in Young Children. NEJM
360: 339-353
[Abstract][Full Text]
Castro, M., Ramirez, M. I., Gern, J. E., Cutting, G., Redding, G., Hagood, J. S., Whitsett, J., Abman, S., Raj, J. U., Barst, R., Kato, G. J., Gozal, D., Haddad, G. G., Prabhakar, N. R., Gauda, E., Martinez, F. D., Tepper, R., Wood, R. E., Accurso, F., Teague, W. G., Venegas, J., Cole, F. S., Wright, R. J.
(2009). Strategic Plan for Pediatric Respiratory Diseases Research: An NHLBI Working Group Report. Proc Am Thorac Soc
6: 1-10
[Abstract][Full Text]
Martel, M.-J., Rey, E., Malo, J.-L., Perreault, S., Beauchesne, M.-F., Forget, A., Blais, L.
(2009). Determinants of the Incidence of Childhood Asthma: A Two-Stage Case-Control Study. Am J Epidemiol
169: 195-205
[Abstract][Full Text]
Llapur, C. J., Martinez, T. M., Coates, C., Tiller, C., Wiebke, J. L., Li, X., Applegate, K., Coxson, H. O., Tepper, R. S.
(2009). Lung structure and function of infants with recurrent wheeze when asymptomatic. Eur Respir J
33: 107-112
[Abstract][Full Text]
Halterman, J S, Lynch, K A, Conn, K M, Hernandez, T E, Perry, T T, Stevens, T P
(2009). Environmental exposures and respiratory morbidity among very low birth weight infants at 1 year of life. Arch. Dis. Child.
94: 28-32
[Abstract][Full Text]
Linnane, B. M., Hall, G. L., Nolan, G., Brennan, S., Stick, S. M., Sly, P. D., Robertson, C. F., Robinson, P. J., Franklin, P. J., Turner, S. W., Ranganathan, S. C., on behalf of the Australian Respiratory Early Surv,
(2008). Lung Function in Infants with Cystic Fibrosis Diagnosed by Newborn Screening. Am. J. Respir. Crit. Care Med.
178: 1238-1244
[Abstract][Full Text]
Bouzigon, E., Corda, E., Aschard, H., Dizier, M.-H., Boland, A., Bousquet, J., Chateigner, N., Gormand, F., Just, J., Le Moual, N., Scheinmann, P., Siroux, V., Vervloet, D., Zelenika, D., Pin, I., Kauffmann, F., Lathrop, M., Demenais, F.
(2008). Effect of 17q21 Variants and Smoking Exposure in Early-Onset Asthma. NEJM
359: 1985-1994
[Abstract][Full Text]
Turner, S. W
(2008). A noisy teenager. BMJ
337: a2289-a2289
[Full Text]
Henderson, A.
(2008). What have we learned from prospective cohort studies of asthma in children?. Chronic Respiratory Disease
5: 225-231
[Abstract]
Kapitein, B., Hoekstra, M. O., Nijhuis, E. H. J., Hijnen, D. J., Arets, H. G. M., Kimpen, J. L. L., Knol, E. F.
(2008). Gene expression in CD4+ T-cells reflects heterogeneity in infant wheezing phenotypes. Eur Respir J
32: 1203-1212
[Abstract][Full Text]
Henderson, J, Granell, R, Heron, J, Sherriff, A, Simpson, A, Woodcock, A, Strachan, D P, Shaheen, S O, Sterne, J A C
(2008). Associations of wheezing phenotypes in the first 6 years of life with atopy, lung function and airway responsiveness in mid-childhood. Thorax
63: 974-980
[Abstract][Full Text]
Brand, P. L. P., Baraldi, E., Bisgaard, H., Boner, A. L., Castro-Rodriguez, J. A., Custovic, A., de Blic, J., de Jongste, J. C., Eber, E., Everard, M. L., Frey, U., Gappa, M., Garcia-Marcos, L., Grigg, J., Lenney, W., Le Souef, P., McKenzie, S., Merkus, P. J. F. M., Midulla, F., Paton, J. Y., Piacentini, G., Pohunek, P., Rossi, G. A., Seddon, P., Silverman, M., Sly, P. D., Stick, S., Valiulis, A., van Aalderen, W. M. C., Wildhaber, J. H., Wennergren, G., Wilson, N., Zivkovic, Z., Bush, A.
(2008). Definition, assessment and treatment of wheezing disorders in preschool children: an evidence-based approach. Eur Respir J
32: 1096-1110
[Abstract][Full Text]
Eigen, H.
(2008). Differential Diagnosis and Treatment of Wheezing and Asthma in Young Children. CLIN PEDIATR
47: 735-743
Jackson, D. J., Gangnon, R. E., Evans, M. D., Roberg, K. A., Anderson, E. L., Pappas, T. E., Printz, M. C., Lee, W.-M., Shult, P. A., Reisdorf, E., Carlson-Dakes, K. T., Salazar, L. P., DaSilva, D. F., Tisler, C. J., Gern, J. E., Lemanske, R. F. Jr.
(2008). Wheezing Rhinovirus Illnesses in Early Life Predict Asthma Development in High-Risk Children. Am. J. Respir. Crit. Care Med.
178: 667-672
[Abstract][Full Text]
Luccioli, S., Ross, M., Labiner-Wolfe, J., Fein, S. B.
(2008). Maternally Reported Food Allergies and Other Food-Related Health Problems in Infants: Characteristics and Associated Factors. Pediatrics
122: S105-S112
[Abstract][Full Text]
Matricardi, P. M., Illi, S., Gruber, C., Keil, T., Nickel, R., Wahn, U., Lau, S.
(2008). Wheezing in childhood: incidence, longitudinal patterns and factors predicting persistence. Eur Respir J
32: 585-592
[Abstract][Full Text]
Turato, G., Barbato, A., Baraldo, S., Zanin, M. E., Bazzan, E., Lokar-Oliani, K., Calabrese, F., Panizzolo, C., Snijders, D., Maestrelli, P., Zuin, R., Fabbri, L. M., Saetta, M.
(2008). Nonatopic Children with Multitrigger Wheezing Have Airway Pathology Comparable to Atopic Asthma. Am. J. Respir. Crit. Care Med.
178: 476-482
[Abstract][Full Text]
Palvo, F., Toledo, E. C., Menin, A. M. C. R., Jorge, P. P. O., Godoy, M. F., Sole, D.
(2008). Risk Factors of Childhood Asthma in Sao Jose do Rio Preto, Sao Paulo, Brazil. J Trop Pediatr
54: 253-257
[Abstract][Full Text]
Turner, S W, Craig, L C A, Harbour, P J, Forbes, S H, McNeill, G, Seaton, A, Devereux, G, Russell, G, Helms, P J
(2008). Early rattles, purrs and whistles as predictors of later wheeze. Arch. Dis. Child.
93: 701-704
[Abstract][Full Text]
Willers, S. M., Wijga, A. H., Brunekreef, B., Kerkhof, M., Gerritsen, J., Hoekstra, M. O., de Jongste, J. C., Smit, H. A.
(2008). Maternal Food Consumption during Pregnancy and the Longitudinal Development of Childhood Asthma. Am. J. Respir. Crit. Care Med.
178: 124-131
[Abstract][Full Text]
Metsala, J., Kilkkinen, A., Kaila, M., Tapanainen, H., Klaukka, T., Gissler, M., Virtanen, S. M.
(2008). Perinatal Factors and the Risk of Asthma in Childhood--A Population-based Register Study in Finland. Am J Epidemiol
168: 170-178
[Abstract][Full Text]
Carroll, K. N., Gebretsadik, T., Griffin, M. R., Wu, P., Dupont, W. D., Mitchel, E. F., Enriquez, R., Hartert, T. V.
(2008). Increasing Burden and Risk Factors for Bronchiolitis-Related Medical Visits in Infants Enrolled in a State Health Care Insurance Plan. Pediatrics
122: 58-64
[Abstract][Full Text]
Smith, J. A., Drake, R., Simpson, A., Woodcock, A., Pickles, A., Custovic, A.
(2008). Dimensions of Respiratory Symptoms in Preschool Children: Population-based Birth Cohort Study. Am. J. Respir. Crit. Care Med.
177: 1358-1363
[Abstract][Full Text]
Tebow, G., Sherrill, D. L., Lohman, I. C., Stern, D. A., Wright, A. L., Martinez, F. D., Halonen, M., Guerra, S.
(2008). Effects of Parental Smoking on Interferon {gamma} Production in Children. Pediatrics
121: e1563-e1569
[Abstract][Full Text]
Spycher, B. D., Silverman, M., Brooke, A. M., Minder, C. E., Kuehni, C. E.
(2008). Distinguishing phenotypes of childhood wheeze and cough using latent class analysis. Eur Respir J
31: 974-981
[Abstract][Full Text]
Turner, S, Zhang, G, Young, S, Cox, M, Goldblatt, J, Landau, L, Le Souef, P
(2008). Associations between postnatal weight gain, change in postnatal pulmonary function, formula feeding and early asthma. Thorax
63: 234-239
[Abstract][Full Text]
Wu, C. A., Peluso, J. J., Shanley, J. D., Puddington, L., Thrall, R. S.
(2008). Murine Cytomegalovirus Influences Foxj1 Expression, Ciliogenesis, and Mucus Plugging in Mice with Allergic Airway Disease. Am. J. Pathol.
172: 714-724
[Abstract][Full Text]
Bateman, E. D., Hurd, S. S., Barnes, P. J., Bousquet, J., Drazen, J. M., FitzGerald, M., Gibson, P., Ohta, K., O'Byrne, P., Pedersen, S. E., Pizzichini, E., Sullivan, S. D., Wenzel, S. E., Zar, H. J.
(2008). Global strategy for asthma management and prevention: GINA executive summary. Eur Respir J
31: 143-178
[Abstract][Full Text]
Fedulov, A. V., Leme, A., Yang, Z., Dahl, M., Lim, R., Mariani, T. J., Kobzik, L.
(2008). Pulmonary Exposure to Particles during Pregnancy Causes Increased Neonatal Asthma Susceptibility. Am. J. Respir. Cell Mol. Bio.
38: 57-67
[Abstract][Full Text]
Devulapalli, C S, Carlsen, K C L, Haland, G, Munthe-Kaas, M C, Pettersen, M, Mowinckel, P, Carlsen, K-H
(2008). Severity of obstructive airways disease by age 2 years predicts asthma at 10 years of age. Thorax
63: 8-13
[Abstract][Full Text]
Salam, M. T., Gauderman, W. J., McConnell, R., Lin, P.-C., Gilliland, F. D.
(2007). Transforming Growth Factor- 1 C-509T Polymorphism, Oxidant Stress, and Early-Onset Childhood Asthma. Am. J. Respir. Crit. Care Med.
176: 1192-1199
[Abstract][Full Text]
Kotaniemi-Syrjanen, A., Malmberg, L. P., Pelkonen, A. S., Malmstrom, K., Makela, M. J.
(2007). Airway responsiveness: associated features in infants with recurrent respiratory symptoms. Eur Respir J
30: 1150-1157
[Abstract][Full Text]
To, T., Gershon, A., Wang, C., Dell, S., Cicutto, L.
(2007). Persistence and Remission in Childhood Asthma: A Population-Based Asthma Birth Cohort Study. Arch Pediatr Adolesc Med
161: 1197-1204
[Abstract][Full Text]
Salam, M. T, Lin, P.-C., Avol, E. L, Gauderman, W J., Gilliland, F. D
(2007). Microsomal epoxide hydrolase, glutathione S-transferase P1, traffic and childhood asthma. Thorax
62: 1050-1057
[Abstract][Full Text]
Guilbert, T. W., Stern, D. A., Morgan, W. J., Martinez, F. D., Wright, A. L.
(2007). Effect of Breastfeeding on Lung Function in Childhood and Modulation by Maternal Asthma and Atopy. Am. J. Respir. Crit. Care Med.
176: 843-848
[Abstract][Full Text]
Saglani, S., Payne, D. N., Zhu, J., Wang, Z., Nicholson, A. G., Bush, A., Jeffery, P. K.
(2007). Early Detection of Airway Wall Remodeling and Eosinophilic Inflammation in Preschool Wheezers. Am. J. Respir. Crit. Care Med.
176: 858-864
[Abstract][Full Text]
Devulapalli, C. S.
(2007). Birth weight and adult lung function. Thorax
62: 1016-1017
[Full Text]
Islam, T., Gauderman, W J., Berhane, K., McConnell, R., Avol, E., Peters, J. M, Gilliland, F. D
(2007). Relationship between air pollution, lung function and asthma in adolescents. Thorax
62: 957-963
[Abstract][Full Text]
Bisgaard, H., Hermansen, M. N., Buchvald, F., Loland, L., Halkjaer, L. B., Bonnelykke, K., Brasholt, M., Heltberg, A., Vissing, N. H., Thorsen, S. V., Stage, M., Pipper, C. B.
(2007). Childhood Asthma after Bacterial Colonization of the Airway in Neonates. NEJM
357: 1487-1495
[Abstract][Full Text]
Kuehni, C. E, Brooke, A. M, Strippoli, M.-P. F, Spycher, B. D, Davis, A., Silverman, M.
(2007). Cohort Profile: The Leicester Respiratory Cohorts. Int J Epidemiol
0: dym090v1-dym090
[Full Text]
Mai, X.-M., Almqvist, C., Nilsson, L., Wickman, M.
(2007). Birth anthropometric measures, body mass index and allergic diseases in a birth cohort study (BAMSE). Arch. Dis. Child.
92: 881-886
[Abstract][Full Text]
Klinnert, M. D., Liu, A. H., Pearson, M. R., Tong, S., Strand, M., Luckow, A., Robinson, J. L.
(2007). Outcome of a Randomized Multifaceted Intervention With Low-Income Families of Wheezing Infants. Arch Pediatr Adolesc Med
161: 783-790
[Abstract][Full Text]
Boyd, J. H., Macklin, E. A., Strunk, R. C., DeBaun, M. R.
(2007). Asthma is associated with Increased mortality in individuals with sickle cell anemia. haematol
92: 1115-1118
[Abstract][Full Text]
Chatzi, L., Apostolaki, G., Bibakis, I., Skypala, I., Bibaki-Liakou, V., Tzanakis, N., Kogevinas, M., Cullinan, P.
(2007). Protective effect of fruits, vegetables and the Mediterranean diet on asthma and allergies among children in Crete. Thorax
62: 677-683
[Abstract][Full Text]
Townshend, J, Hails, S, Mckean, M
(2007). Diagnosis of asthma in children. BMJ
335: 198-202
[Full Text]
Lester, M. R.
(2007). Analysis of Steroid Treatment of First Wheezing Episode. AAP Grand Rounds
18: 6-7
[Full Text]
Beydon, N., Davis, S. D., Lombardi, E., Allen, J. L., Arets, H. G. M., Aurora, P., Bisgaard, H., Davis, G. M., Ducharme, F. M., Eigen, H., Gappa, M., Gaultier, C., Gustafsson, P. M., Hall, G. L., Hantos, Z., Healy, M. J. R., Jones, M. H., Klug, B., Lodrup Carlsen, K. C., McKenzie, S. A., Marchal, F., Mayer, O. H., Merkus, P. J. F. M., Morris, M. G., Oostveen, E., Pillow, J. J., Seddon, P. C., Silverman, M., Sly, P. D., Stocks, J., Tepper, R. S., Vilozni, D., Wilson, N. M., on behalf of the American Thoracic Society/Europea,
(2007). An Official American Thoracic Society/European Respiratory Society Statement: Pulmonary Function Testing in Preschool Children. Am. J. Respir. Crit. Care Med.
175: 1304-1345
[Full Text]
Panitch, H. B.
(2007). The Relationship Between Early Respiratory Viral Infections and Subsequent Wheezing and Asthma. CLIN PEDIATR
46: 392-400
Pereira, M. U., Sly, P. D., Pitrez, P. M., Jones, M. H., Escouto, D., Dias, A. C. O., Weiland, S. K., Stein, R. T.
(2007). Nonatopic asthma is associated with helminth infections and bronchiolitis in poor children. Eur Respir J
29: 1154-1160
[Abstract][Full Text]
Caudri, D., Wijga, A., Gehring, U., Smit, H. A., Brunekreef, B., Kerkhof, M., Hoekstra, M., Gerritsen, J., de Jongste, J. C.
(2007). Respiratory Symptoms in the First 7 Years of Life and Birth Weight at Term: The PIAMA Birth Cohort. Am. J. Respir. Crit. Care Med.
175: 1078-1085
[Abstract][Full Text]
Lloyd, C. M., Robinson, D. S.
(2007). Allergen-induced airway remodelling. Eur Respir J
29: 1020-1032
[Abstract][Full Text]
Moore, W. C., Peters, S. P.
(2007). Update in Asthma 2006. Am. J. Respir. Crit. Care Med.
175: 649-654
[Full Text]
Camargo, C. A Jr, Rifas-Shiman, S. L, Litonjua, A. A, Rich-Edwards, J. W, Weiss, S. T, Gold, D. R, Kleinman, K., Gillman, M. W
(2007). Maternal intake of vitamin D during pregnancy and risk of recurrent wheeze in children at 3 y of age. Am. J. Clin. Nutr.
85: 788-795
[Abstract][Full Text]
Devereux, G., Litonjua, A. A, Turner, S. W, Craig, L. C., McNeill, G., Martindale, S., Helms, P. J, Seaton, A., Weiss, S. T
(2007). Maternal vitamin D intake during pregnancy and early childhood wheezing. Am. J. Clin. Nutr.
85: 853-859
[Abstract][Full Text]
Pekkanen, J., Hyvarinen, A., Haverinen-Shaughnessy, U., Korppi, M., Putus, T., Nevalainen, A.
(2007). Moisture damage and childhood asthma: a population-based incident case-control study. Eur Respir J
29: 509-515
[Abstract][Full Text]
Berz, J. B., Carter, A. S., Wagmiller, R. L., Horwitz, S. M., Murdock, K. K., Briggs-Gowan, M.
(2007). Prevalence and Correlates of Early Onset Asthma and Wheezing in a Healthy Birth Cohort of 2- to 3-Year Olds. J Pediatr Psychol
32: 154-166
[Abstract][Full Text]
Zar, H J, Streun, S, Levin, M, Weinberg, E G, Swingler, G H
(2007). Randomised controlled trial of the efficacy of a metered dose inhaler with bottle spacer for bronchodilator treatment in acute lower airway obstruction. Arch. Dis. Child.
92: 142-146
[Abstract][Full Text]
Singh, A. M., Moore, P. E., Gern, J. E., Lemanske, R. F. Jr., Hartert, T. V.
(2007). Bronchiolitis to Asthma: A Review and Call for Studies of Gene-Virus Interactions in Asthma Causation. Am. J. Respir. Crit. Care Med.
175: 108-119
[Abstract][Full Text]
Martinez, F. D.
(2007). Genes, environments, development and asthma: a reappraisal. Eur Respir J
29: 179-184
[Abstract][Full Text]
Tahan, F., Ozcan, A., Koc, N.
(2007). Clarithromycin in the treatment of RSV bronchiolitis: a double-blind, randomised, placebo-controlled trial. Eur Respir J
29: 91-97
[Abstract][Full Text]
Rusconi, F., Galassi, C., Forastiere, F., Bellasio, M., De Sario, M., Ciccone, G., Brunetti, L., Chellini, E., Corbo, G., La Grutta, S., Lombardi, E., Piffer, S., Talassi, F., Biggeri, A., Pearce, N., the SIDRIA-2 Collaborative Group,
(2007). Maternal Complications and Procedures in Pregnancy and at Birth and Wheezing Phenotypes in Children. Am. J. Respir. Crit. Care Med.
175: 16-21
[Abstract][Full Text]
Ly, N. P., Rifas-Shiman, S. L., Litonjua, A. A., Tzianabos, A. O., Schaub, B., Ruiz-Perez, B., Tantisira, K. G., Finn, P. W., Gillman, M. W., Weiss, S. T., Gold, D. R.
(2007). Cord Blood Cytokines and Acute Lower Respiratory Illnesses in the First Year of Life. Pediatrics
119: e171-e178
[Abstract][Full Text]
Proud, D., Chow, C.-W.
(2006). Role of Viral Infections in Asthma and Chronic Obstructive Pulmonary Disease. Am. J. Respir. Cell Mol. Bio.
35: 513-518
[Abstract][Full Text]
