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Trends in eczema, rhinitis, and rye grass sensitization in a longitudinal asthma cohort
Ann Allergy Asthma Immunol 112 (2014) 437e440
Contents lists available at ScienceDirect
Trends in eczema, rhinitis, and rye grass sensitization in a longitudinal asthma cohort Andrew Tai, MBBS, PhD *; Haily Tran, BBiomedSc y; Mary Roberts, BSc z; Nadeene Clarke, BSc y; John Wilson, MBBS, PhD x; and Colin F. Robertson, MBBS, MD z * Department
of Respiratory and Sleep Medicine, Women’s and Children’ Hospital, North Adelaide, South Australia, Australia Murdoch Children’s Research Institute, Parkville, Victoria, Australia z Royal Children’s Hospital Melbourne, Parkville, Victoria, Australia x Department of Allergy, Immunology and Respiratory Medicine, The Alfred Hospital, Prahran, Victoria, Australia y
A R T I C L E
I N F O
Article history: Received for publication January 13, 2014. Received in revised form February 21, 2014. Accepted for publication March 10, 2014.
A B S T R A C T
Background: Atopic conditions are prevalent in the Western world, with limited long-term data on atopic trends in patients with asthma. Objective: To describe the trends in eczema, rhinitis, and allergic sensitization in a longitudinal childhood asthma cohort. Methods: Four hundred eighty-four patients were recruited at 7 years of age and followed regularly to 50 years of age. Subjects completed an interviewer-administered questionnaire to define current eczema and rhinitis. Skin prick testing to rye grass also was performed. Results: The participation rate over the past 4 decades has been maintained at 72% to 91%. There was a decrease in the prevalence of eczema in the past 12 months in groups with viral-associated wheeze (21% to 8%, P ¼ .002), asthma (47% to 18%, P < .001), and severe asthma (69% to 28%, P < .001) from 14 to 21 years of age. Conversely, there was an increase in the prevalence of rhinitis in the previous 12 months in groups without asthma (1% to 6%, P ¼ .04; 1% to 20%, P ¼ .008), with viral-associated wheeze (16% to 28%, P ¼ .006; 16% to 49%, P < .001), and with asthma (45% to 56%, P ¼ .2; 45% to 73%, P ¼ .014) from recruitment to 10 and 14 years of age, respectively. There were 2 peaks in prevalence in the sensitization to rye grass in this cohort from 7 to 10 years of age and from 14 to 21 years of age in all groups. Conclusion: The adolescence phase appears to be an important period in the body’s response to allergens whereby eczema decreases in prevalence, whereas rhinitis and rye grass sensitization increase in prevalence. Ó 2014 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.
Introduction Atopy or allergic disorders are common and have been closely related to the increase in asthma in the past few decades.1e3 A recent study of a Tasmanian birth cohort showed an association between childhood allergic rhinitis and an increased risk of developing new-onset asthma in preadolescence, adolescence, and adulthood.4 There have been several cross-sectional studies that have described an increase in atopic prevalence,1,2 and it is notably highest in Western developed countries.5 Longitudinal studies on the natural progression of atopy from birth cohorts to childhood years6,7 and to early adult life8 have been described. There are currently no studies to describe the outcome of atopy and allergic disorders from childhood well into adulthood. Reprints: Andrew Tai, MBBS, PhD, Department of Respiratory and Sleep Medicine, Women’s and Children’ Hospital, 72 King William Road, North Adelaide 5006, SA, Australia; E-mail: [email protected]. Disclosure: Authors have nothing to report. Funding: This study was funded by the National Medical Health Research Council, Australia.
The Melbourne Asthma Study was commenced in 1964 to describe the spectrum and natural outcome of childhood asthma and wheezy bronchitis.9 This study has been conducted at 7-year intervals from 7 to 42 years pf age9e15 and to the current follow-up at 50 years of age. As part of the study, measurements of atopy have been consistently evaluated, which include the presence of rhinitis, eczema, and skin prick testing as an objective measurement of atopy. Data on atopy have been presented at 7 and 35 years of age,9,16 but there has been no longitudinal analysis of the data published to date. In the original study, it was not surprising that the prevalence of eczema, rhinitis, and rye grass sensitization was highest in the severe asthma group compared with those with mild or no asthma.9 In the assessment at 35 years of age, the presence of an atopic condition defined by the presence of rhinitis, eczema, or skin test reactivity (rye grass) was found to increase the odds of more severe asthma in later life.16 Therefore, the aim of this study was to describe the longitudinal prevalence of eczema, rhinitis, and rye grass sensitization from childhood into adulthood in this prospective asthma cohort.
1081-1206/14/$36.00 - see front matter Ó 2014 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.anai.2014.03.005
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A. Tai et al. / Ann Allergy Asthma Immunol 112 (2014) 437e440
Table 1 Participation rate of subjects from recruitment, at varying ages to 50 years old Groups
Recruitment, n (%)
Subjects at each age of participation, n (% total) 10 y
C VAW A SA
105 (22) 178 (37) 113 (24) 83 (17) 479a
83 170 100 83 436
14 y (19) (39) (23) (19) (91)
78 130 84 61 353
21 y (22) (37) (24) (17) (74)
81 151 98 69 399
28 y (20) (38) (25) (17) (83)
72 136 92 61 361
35 y (20) (38) (25) (17) (75)
85 141 94 63 393
42 y (22) (39) (24) (16) (82)
86 149 98 70 403
50 y (21) (37) (24) (17) (84)
77 128 81 60 346
(22) (36) (23) (17) (72)
Abbreviations: A, asthma; C, control (no asthma); SA, severe asthma; VAW, viral-associated wheeze. a Five original records lost.
Methods Cohort A modified random sampling strategy was used to select 401 subjects after a survey of 30,000 grade 2 Melbourne primary school children in 1963 to 1964. The survey included a parent-completed questionnaire, which was followed by a parent interview and physical examination of the child by members of the research team. All those children with a history of asthma or wheezy bronchitis were included in the study, and 1 in 2 with mild wheezy bronchitis and 1 in 20 controls were included. When the children were reviewed at 10 years of age, it was realized that there were very few with severe asthma, and a further sampling of 21,000 children was performed from the same birth cohort to establish a severe asthma group. The original groups were classified as follows:
past 12 months. Patients who were not able to present to the hospital had the questionnaire administered by telephone. The questionnaire was applied in person or by telephone by a consistent member of the research team at each study review. Skin Prick Test Assessment Skin prick testing was performed as an objective measurement of atopic status. A positive response to a particular challenge was defined as a wheal with a diameter at least 3 mm larger than the diameter of a wheal from a negative control. The allergen that was consistently used throughout the study periods was rye grass. Other allergens were used at varying assessments but excluded from the analysis owing to a lack of consistency. Positive (histamine) and negative (saline/glycerin) controls also were tested. Before testing, antihistamines were withheld for 72 hours. Statistical Analysis
1. Control (without asthma)d105 children who had never wheezed. 2. Mild wheezy bronchitisd74 children with fewer than 5 episodes of wheezing associated with bronchitis or respiratory tract infection. 3. Wheezy bronchitisd104 children with at least 5 episodes of wheezing associated with bronchitis or respiratory tract infection. 4. Asthmad113 children with wheezing not associated with respiratory tract infection. 5. Severe asthma (SA)d83 children with onset of symptoms before 3 years of age; at least 10 attacks in the 2 years before 10 years of age or persistent symptoms at 10 years of age; and barrel-chest deformity and/or decrease of the ratio of forced expiratory volume in 1 second to forced vital capacity to 50% or less or some combination of these factors. For this study, the mild wheezy bronchitis and wheezy bronchitis groups were combined because they represented children with viral-associated wheeze (VAW). All surviving members from the original cohort were contacted and asked to present to the Royal Children’s Hospital respiratory department to complete an assessment consisting of an intervieweradministered questionnaire, lung function testing, and skin prick testing. These assessments have occurred at 7-year intervals from 7 to 42 years of age and then to the present study, when subjects were 50 years of age. Interviewer-Administered Questionnaire An interviewer-administered questionnaire performed during the study periods collected details on the frequency of wheeze, frequency of rhinitis, and eczema symptoms. Eczema was defined in children or adults as symptoms of dry, itchy rash localized to flexural regions (such as folds of the elbows, behind the knees), facial, or generalized to the body in the past 12 months. Rhinitis was defined in children or adults as symptoms of sneezing, nasal itching, or a runny or blocked nose in the absence of a cold or flu in the
Data analysis was performed using Stata 10.0 for Windows (Stata Corp, College Station, Texas). Clinical outcomes and prevalence measurements were described as percentages over the different study periods. Chi-square testing was applied to measure the change in prevalence between 2 subsequent time points. This study was approved by the human research ethics committee at the Royal Children’s Hospital Melbourne. Oral and written consents were obtained from participating subjects. Results Participation Rate at Each Assessment Period from Recruitment to 50 Years of Age The participation rate over the course of the study has ranged from 72% to 91% (Table 1), with good representation of the original groups at each review. Of the original 484 participants, 5 original records were lost. Trend in Eczema over Study Periods by Recruitment Groups At the time of recruitment, the prevalence of eczema in the previous 12 months was least in the control group (10%), with increases in the VAW (17%) and asthma (41%) groups. At 10 years of age, the prevalence in the SA group was 67%. The prevalence of eczema in the nonasthmatic group remained similar throughout the study periods (range 8%e14%). From 14 to 21 years of age, there was a decrease in the prevalence of eczema in the VAW (21% to 8%, P ¼ .002), asthma (47% to 18%, P < .001), and SA (69% to 28%, P < .001) groups. The prevalence of eczema appeared to plateau in all groups after 21 years of age (Fig 1). Trend in Rhinitis over Study Periods by Recruitment Groups At the time of recruitment, the prevalence of rhinitis in the previous 12 months was least in the control group (1%), with increases in the VAW (16%) and asthma (45%) groups. At 10 years of age, the prevalence in the SA group was 65%. In the nonasthmatic
A. Tai et al. / Ann Allergy Asthma Immunol 112 (2014) 437e440
Figure 1. Prevalence of eczema in the past 12 months at each period by recruitment groups (*P < .05, **P < .001). A, asthma; C, control (no asthma); SA, severe asthma; VAW, viral-associated wheeze.
group, the prevalence of rhinitis increased from recruitment to 10 and 14 years of age, respectively (1% to 6%, P ¼ .04; 1% to 20%, P ¼ .008). A similar pattern was noted for those in the VAW group, with an increase from the recruitment group to 10 and 14 years of age (16% to 28%, P ¼ .006; 16% to 49%, P < .001; asthma group: 45% to 56%, P ¼ .2; 45% to 73%, P ¼ .014). In the SA group, the prevalence of rhinitis was high throughout the study period (ranging from 65% at recruitment to a peak of 84% at 35 years of age). The prevalence of rhinitis appeared to plateau in all groups after 21 years of age (Fig 2). Trend in Rye Grass Sensitization over Study Periods by Recruitment Groups At the time of recruitment, the prevalence of rye grass sensitization was least in the nonasthmatic group (3%), with increases in the VAW (14%) and asthma (37%) groups. At 10 years of age, the prevalence in the SA group was 45%. In all groups, there appeared to be increase in prevalence in rye grass sensitization rates from 7 to 10 years of age and from 14 to 21 years of age. In the nonasthmatic group, the prevalence of rye grass sensitization increased from recruitment to 10 years of age (3% to 13%, P ¼ .005), decreased to 14 years of age (13% to 2%, P ¼ .009), and increased again to 21 years of age (2% to 12%, P ¼ .02). In the VAW group, there was an increase from the recruitment group to 10 years of age (14% to 22%, P ¼ .04) and from 14 to 21 years of age (23% to 35%, P ¼ .03). Similar patterns were noted in the asthma group, with an increase from recruitment
Figure 2. Prevalence of allergic rhinitis in the past 12 months at each period by recruitment groups (*P < .05, **P < .01). A, asthma; C, control (no asthma); SA, severe asthma; VAW, viral-associated wheeze.
439
Figure 3. Prevalence of rye grass sensitization at each period by recruitment groups (*P < .05, **P < .01). A, asthma; C, control (no asthma); SA, severe asthma; VAW, viralassociated wheeze.
to 10 years of age (37% to 61%, P ¼ .008) and from 14 to 21 years of age (51% to 71%, P ¼ .007). In the SA group, an increase was noted from 14 to 21 years of age (42% to 68%, P ¼ .003), with a peak of 81% at 35 years of age. The prevalence of rye grass sensitization appeared to plateau in all groups after 21 years of age (Fig 3). Discussion The period of adolescence appeared to be an important phase in the expression of eczema, rhinitis, and rye grass sensitization in this asthma cohort. There was an increase in the prevalence of rhinitis leading into adolescence in the nonasthmatic, VAW, and asthma groups, whereas there was a decrease in prevalence of eczema in children with VAW and asthma. In the present cohort, there also was an increasing prevalence to rye grass sensitization across all groups from 7 to 10 years of age and from adolescence to 21 years of age. There are no clear reasons to define this trend that was seen in the adolescence phase. The authors can only speculate that there may be potential hormonal and immunomodulatory factors or a response to the environment occurring in association with puberty that may predispose toward this increase in rhinitis and rye grass sensitization and resolution of eczema. It would be important to define these mechanisms, recognizing the clear association between eczema and the incidence of asthma throughout adult life, and the risk of allergic rhinitis as a predictor of asthma persistence into adult life.4,17 There are several limitations to this study. First, a lack of clinical information and objective measurements of atopy before 7 years of age may incorrectly define the atopic patterns in this study group because many children with eczema have been described to have undergone remission by 3 years of age.6 Second, potential confounders, such as parental atopy, breastfeeding in infancy, treatment methods (such as desensitization techniques), and environmental influences (such as geographic residence), have not been measured. Third, the authors acknowledge that Australia has a high prevalence of allergic disease and this finding may be limited to Western countries. Fourth, because rye grass was the only consistent allergen measured in the study, the actual prevalence of sensitization may be underestimated. Fifth, the authors have not characterized allergic rhinitis because skin prick testing across the ages varied and were not consistent apart from rye grass. Sixth, given that there was subject attendance variation between each study period, the prevalence measurements would vary to a degree. Seventh, information by questionnaire is clearly subject to recall bias. Nevertheless, the long-term prospective nature of this study, high participation rate across the past 4 decades, and good representation of the original cohort at each assessment period support the trends the authors observed in this well-characterized asthma cohort.
440
A. Tai et al. / Ann Allergy Asthma Immunol 112 (2014) 437e440
In conclusion, the period of adolescence appeared to be an important phase in this longitudinal asthma cohort whereby eczema prevalence decreased and rhinitis and rye grass sensitization increased. Therefore, attention should be focused on this phase of adolescence to clarify mechanisms to explain the body’s changing response to these disorders. This may lead to treatment options that might modify the incidence and persistence of asthma into adult life. References [1] Downs SH, Marks GB, Sporik R, Belosouva EG, Car NG, Peat JK. Continued increase in the prevalence of asthma and atopy. Arch Dis Child. 2001;84: 20e23. [2] Nina TK, Russell G. Respiratory symptoms and atopy in Aberdeen school children: evidence from two surveys 25 years apart. BMJ. 1992;304:873e875. [3] Peat JK, Salome CM, Woolcock AJ. Longitudinal changes in atopy during a 4 year period: Relation to bronchial hyperresponsiveness and respiratory symptoms in a population sample of Australian schoolchildren. J Allergy Clin Immunol. 1990;85:65e74. [4] Burgess JA, Walters EH, Byrnes GB, et al. Childhood allergic rhinitis predicts asthma incidence and persistence to middle age: a longitudinal study. J Allergy Clin Immunol. 2007;120:863e869. [5] Asher MI, Montefort S, Bjorksten B, et al. Worldwide time trends in the prevalence of symptoms of asthma, allergic rhinoconjunctivitis and eczema in childhood: ISAAC Phases One and Three repeat multi-country cross-sectional surveys. Lancet. 2006;368:733e743.
[6] Illi S, Von Mutius E, Lau S, et al. The natural course of atopic dermatitis from birth to age 7 years and the association with asthma. J Allergy Clin Immunol. 2004;113:925e931. [7] Tariq SM, Matthews S, Hakim EA, Stevens M, Arshad SH, Hide DW. The prevalence of and risk factors for atopy in early childhood: a whole population birth cohort study. J Allergy Clin Immunol. 1998;101:587e593. [8] Rhodes HL, Thomas PS, Sporik R, Holgate ST, Cogswell JJ. A birth cohort study of subjects at risk of atopy: twenty-two year follow-up of wheeze and atopic status. Am J Respir Crit Care Med. 2002;165:176e180. [9] Williams H, McNicol KN. Prevalence, natural history, and relationship of wheezy bronchitis and asthma in children. An epidemiological study. BMJ. 1969;4:321e325. [10] Horak E, Lanigan A, Roberts M, et al. Longitudinal study of childhood wheezy bronchitis and asthma: outcome at age 42. BMJ. 2003;326:422e423. [11] Kelly WJW, Hudson I, Phelan PD, Pain MC, Olinsky A. Childhood asthma in adult life: a further study at 28 years of age. BMJ. 1987;294:1059e1062. [12] Martin AJ, McLennan LA, Landau LI, Phelan PD. The natural history of childhood asthma to adult life. BMJ. 1980;280:1397e1400. [13] McNicol KN, Williams H. Spectrum of asthma in childrendclinical and physiological components. BMJ. 1973;4:7e11. [14] Oswald H, Phelan PD, Lanigan A, Hibbert M, Carlin JB, Bowes G. Childhood asthma and lung function in mid-adult life. Pediatr Pulmonol. 1997;23:14e20. [15] Phelan PD, Robertson CF, Olinsky A. The Melbourne Asthma Study: 1964e1999. J Allergy Clin Immunol. 2002;109:189e194. [16] Wolfe R, Carlin JB, Oswald H, Olinsky A, Phelan PD, Robertson CF. Association between allergy and asthma from childhood to middle adulthood in an Australian cohort study. Am J Respir Crit Care Med. 2000;162:2177e2181. [17] Strachan DP, Butland BK, Anderson HR. Incidence and prognosis of asthma and wheezing illness from early childhood to age 33 in a national British cohort. BMJ. 1996;312:1195e1199.
Contents lists available at ScienceDirect
Trends in eczema, rhinitis, and rye grass sensitization in a longitudinal asthma cohort Andrew Tai, MBBS, PhD *; Haily Tran, BBiomedSc y; Mary Roberts, BSc z; Nadeene Clarke, BSc y; John Wilson, MBBS, PhD x; and Colin F. Robertson, MBBS, MD z * Department
of Respiratory and Sleep Medicine, Women’s and Children’ Hospital, North Adelaide, South Australia, Australia Murdoch Children’s Research Institute, Parkville, Victoria, Australia z Royal Children’s Hospital Melbourne, Parkville, Victoria, Australia x Department of Allergy, Immunology and Respiratory Medicine, The Alfred Hospital, Prahran, Victoria, Australia y
A R T I C L E
I N F O
Article history: Received for publication January 13, 2014. Received in revised form February 21, 2014. Accepted for publication March 10, 2014.
A B S T R A C T
Background: Atopic conditions are prevalent in the Western world, with limited long-term data on atopic trends in patients with asthma. Objective: To describe the trends in eczema, rhinitis, and allergic sensitization in a longitudinal childhood asthma cohort. Methods: Four hundred eighty-four patients were recruited at 7 years of age and followed regularly to 50 years of age. Subjects completed an interviewer-administered questionnaire to define current eczema and rhinitis. Skin prick testing to rye grass also was performed. Results: The participation rate over the past 4 decades has been maintained at 72% to 91%. There was a decrease in the prevalence of eczema in the past 12 months in groups with viral-associated wheeze (21% to 8%, P ¼ .002), asthma (47% to 18%, P < .001), and severe asthma (69% to 28%, P < .001) from 14 to 21 years of age. Conversely, there was an increase in the prevalence of rhinitis in the previous 12 months in groups without asthma (1% to 6%, P ¼ .04; 1% to 20%, P ¼ .008), with viral-associated wheeze (16% to 28%, P ¼ .006; 16% to 49%, P < .001), and with asthma (45% to 56%, P ¼ .2; 45% to 73%, P ¼ .014) from recruitment to 10 and 14 years of age, respectively. There were 2 peaks in prevalence in the sensitization to rye grass in this cohort from 7 to 10 years of age and from 14 to 21 years of age in all groups. Conclusion: The adolescence phase appears to be an important period in the body’s response to allergens whereby eczema decreases in prevalence, whereas rhinitis and rye grass sensitization increase in prevalence. Ó 2014 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.
Introduction Atopy or allergic disorders are common and have been closely related to the increase in asthma in the past few decades.1e3 A recent study of a Tasmanian birth cohort showed an association between childhood allergic rhinitis and an increased risk of developing new-onset asthma in preadolescence, adolescence, and adulthood.4 There have been several cross-sectional studies that have described an increase in atopic prevalence,1,2 and it is notably highest in Western developed countries.5 Longitudinal studies on the natural progression of atopy from birth cohorts to childhood years6,7 and to early adult life8 have been described. There are currently no studies to describe the outcome of atopy and allergic disorders from childhood well into adulthood. Reprints: Andrew Tai, MBBS, PhD, Department of Respiratory and Sleep Medicine, Women’s and Children’ Hospital, 72 King William Road, North Adelaide 5006, SA, Australia; E-mail: [email protected]. Disclosure: Authors have nothing to report. Funding: This study was funded by the National Medical Health Research Council, Australia.
The Melbourne Asthma Study was commenced in 1964 to describe the spectrum and natural outcome of childhood asthma and wheezy bronchitis.9 This study has been conducted at 7-year intervals from 7 to 42 years pf age9e15 and to the current follow-up at 50 years of age. As part of the study, measurements of atopy have been consistently evaluated, which include the presence of rhinitis, eczema, and skin prick testing as an objective measurement of atopy. Data on atopy have been presented at 7 and 35 years of age,9,16 but there has been no longitudinal analysis of the data published to date. In the original study, it was not surprising that the prevalence of eczema, rhinitis, and rye grass sensitization was highest in the severe asthma group compared with those with mild or no asthma.9 In the assessment at 35 years of age, the presence of an atopic condition defined by the presence of rhinitis, eczema, or skin test reactivity (rye grass) was found to increase the odds of more severe asthma in later life.16 Therefore, the aim of this study was to describe the longitudinal prevalence of eczema, rhinitis, and rye grass sensitization from childhood into adulthood in this prospective asthma cohort.
1081-1206/14/$36.00 - see front matter Ó 2014 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.anai.2014.03.005
438
A. Tai et al. / Ann Allergy Asthma Immunol 112 (2014) 437e440
Table 1 Participation rate of subjects from recruitment, at varying ages to 50 years old Groups
Recruitment, n (%)
Subjects at each age of participation, n (% total) 10 y
C VAW A SA
105 (22) 178 (37) 113 (24) 83 (17) 479a
83 170 100 83 436
14 y (19) (39) (23) (19) (91)
78 130 84 61 353
21 y (22) (37) (24) (17) (74)
81 151 98 69 399
28 y (20) (38) (25) (17) (83)
72 136 92 61 361
35 y (20) (38) (25) (17) (75)
85 141 94 63 393
42 y (22) (39) (24) (16) (82)
86 149 98 70 403
50 y (21) (37) (24) (17) (84)
77 128 81 60 346
(22) (36) (23) (17) (72)
Abbreviations: A, asthma; C, control (no asthma); SA, severe asthma; VAW, viral-associated wheeze. a Five original records lost.
Methods Cohort A modified random sampling strategy was used to select 401 subjects after a survey of 30,000 grade 2 Melbourne primary school children in 1963 to 1964. The survey included a parent-completed questionnaire, which was followed by a parent interview and physical examination of the child by members of the research team. All those children with a history of asthma or wheezy bronchitis were included in the study, and 1 in 2 with mild wheezy bronchitis and 1 in 20 controls were included. When the children were reviewed at 10 years of age, it was realized that there were very few with severe asthma, and a further sampling of 21,000 children was performed from the same birth cohort to establish a severe asthma group. The original groups were classified as follows:
past 12 months. Patients who were not able to present to the hospital had the questionnaire administered by telephone. The questionnaire was applied in person or by telephone by a consistent member of the research team at each study review. Skin Prick Test Assessment Skin prick testing was performed as an objective measurement of atopic status. A positive response to a particular challenge was defined as a wheal with a diameter at least 3 mm larger than the diameter of a wheal from a negative control. The allergen that was consistently used throughout the study periods was rye grass. Other allergens were used at varying assessments but excluded from the analysis owing to a lack of consistency. Positive (histamine) and negative (saline/glycerin) controls also were tested. Before testing, antihistamines were withheld for 72 hours. Statistical Analysis
1. Control (without asthma)d105 children who had never wheezed. 2. Mild wheezy bronchitisd74 children with fewer than 5 episodes of wheezing associated with bronchitis or respiratory tract infection. 3. Wheezy bronchitisd104 children with at least 5 episodes of wheezing associated with bronchitis or respiratory tract infection. 4. Asthmad113 children with wheezing not associated with respiratory tract infection. 5. Severe asthma (SA)d83 children with onset of symptoms before 3 years of age; at least 10 attacks in the 2 years before 10 years of age or persistent symptoms at 10 years of age; and barrel-chest deformity and/or decrease of the ratio of forced expiratory volume in 1 second to forced vital capacity to 50% or less or some combination of these factors. For this study, the mild wheezy bronchitis and wheezy bronchitis groups were combined because they represented children with viral-associated wheeze (VAW). All surviving members from the original cohort were contacted and asked to present to the Royal Children’s Hospital respiratory department to complete an assessment consisting of an intervieweradministered questionnaire, lung function testing, and skin prick testing. These assessments have occurred at 7-year intervals from 7 to 42 years of age and then to the present study, when subjects were 50 years of age. Interviewer-Administered Questionnaire An interviewer-administered questionnaire performed during the study periods collected details on the frequency of wheeze, frequency of rhinitis, and eczema symptoms. Eczema was defined in children or adults as symptoms of dry, itchy rash localized to flexural regions (such as folds of the elbows, behind the knees), facial, or generalized to the body in the past 12 months. Rhinitis was defined in children or adults as symptoms of sneezing, nasal itching, or a runny or blocked nose in the absence of a cold or flu in the
Data analysis was performed using Stata 10.0 for Windows (Stata Corp, College Station, Texas). Clinical outcomes and prevalence measurements were described as percentages over the different study periods. Chi-square testing was applied to measure the change in prevalence between 2 subsequent time points. This study was approved by the human research ethics committee at the Royal Children’s Hospital Melbourne. Oral and written consents were obtained from participating subjects. Results Participation Rate at Each Assessment Period from Recruitment to 50 Years of Age The participation rate over the course of the study has ranged from 72% to 91% (Table 1), with good representation of the original groups at each review. Of the original 484 participants, 5 original records were lost. Trend in Eczema over Study Periods by Recruitment Groups At the time of recruitment, the prevalence of eczema in the previous 12 months was least in the control group (10%), with increases in the VAW (17%) and asthma (41%) groups. At 10 years of age, the prevalence in the SA group was 67%. The prevalence of eczema in the nonasthmatic group remained similar throughout the study periods (range 8%e14%). From 14 to 21 years of age, there was a decrease in the prevalence of eczema in the VAW (21% to 8%, P ¼ .002), asthma (47% to 18%, P < .001), and SA (69% to 28%, P < .001) groups. The prevalence of eczema appeared to plateau in all groups after 21 years of age (Fig 1). Trend in Rhinitis over Study Periods by Recruitment Groups At the time of recruitment, the prevalence of rhinitis in the previous 12 months was least in the control group (1%), with increases in the VAW (16%) and asthma (45%) groups. At 10 years of age, the prevalence in the SA group was 65%. In the nonasthmatic
A. Tai et al. / Ann Allergy Asthma Immunol 112 (2014) 437e440
Figure 1. Prevalence of eczema in the past 12 months at each period by recruitment groups (*P < .05, **P < .001). A, asthma; C, control (no asthma); SA, severe asthma; VAW, viral-associated wheeze.
group, the prevalence of rhinitis increased from recruitment to 10 and 14 years of age, respectively (1% to 6%, P ¼ .04; 1% to 20%, P ¼ .008). A similar pattern was noted for those in the VAW group, with an increase from the recruitment group to 10 and 14 years of age (16% to 28%, P ¼ .006; 16% to 49%, P < .001; asthma group: 45% to 56%, P ¼ .2; 45% to 73%, P ¼ .014). In the SA group, the prevalence of rhinitis was high throughout the study period (ranging from 65% at recruitment to a peak of 84% at 35 years of age). The prevalence of rhinitis appeared to plateau in all groups after 21 years of age (Fig 2). Trend in Rye Grass Sensitization over Study Periods by Recruitment Groups At the time of recruitment, the prevalence of rye grass sensitization was least in the nonasthmatic group (3%), with increases in the VAW (14%) and asthma (37%) groups. At 10 years of age, the prevalence in the SA group was 45%. In all groups, there appeared to be increase in prevalence in rye grass sensitization rates from 7 to 10 years of age and from 14 to 21 years of age. In the nonasthmatic group, the prevalence of rye grass sensitization increased from recruitment to 10 years of age (3% to 13%, P ¼ .005), decreased to 14 years of age (13% to 2%, P ¼ .009), and increased again to 21 years of age (2% to 12%, P ¼ .02). In the VAW group, there was an increase from the recruitment group to 10 years of age (14% to 22%, P ¼ .04) and from 14 to 21 years of age (23% to 35%, P ¼ .03). Similar patterns were noted in the asthma group, with an increase from recruitment
Figure 2. Prevalence of allergic rhinitis in the past 12 months at each period by recruitment groups (*P < .05, **P < .01). A, asthma; C, control (no asthma); SA, severe asthma; VAW, viral-associated wheeze.
439
Figure 3. Prevalence of rye grass sensitization at each period by recruitment groups (*P < .05, **P < .01). A, asthma; C, control (no asthma); SA, severe asthma; VAW, viralassociated wheeze.
to 10 years of age (37% to 61%, P ¼ .008) and from 14 to 21 years of age (51% to 71%, P ¼ .007). In the SA group, an increase was noted from 14 to 21 years of age (42% to 68%, P ¼ .003), with a peak of 81% at 35 years of age. The prevalence of rye grass sensitization appeared to plateau in all groups after 21 years of age (Fig 3). Discussion The period of adolescence appeared to be an important phase in the expression of eczema, rhinitis, and rye grass sensitization in this asthma cohort. There was an increase in the prevalence of rhinitis leading into adolescence in the nonasthmatic, VAW, and asthma groups, whereas there was a decrease in prevalence of eczema in children with VAW and asthma. In the present cohort, there also was an increasing prevalence to rye grass sensitization across all groups from 7 to 10 years of age and from adolescence to 21 years of age. There are no clear reasons to define this trend that was seen in the adolescence phase. The authors can only speculate that there may be potential hormonal and immunomodulatory factors or a response to the environment occurring in association with puberty that may predispose toward this increase in rhinitis and rye grass sensitization and resolution of eczema. It would be important to define these mechanisms, recognizing the clear association between eczema and the incidence of asthma throughout adult life, and the risk of allergic rhinitis as a predictor of asthma persistence into adult life.4,17 There are several limitations to this study. First, a lack of clinical information and objective measurements of atopy before 7 years of age may incorrectly define the atopic patterns in this study group because many children with eczema have been described to have undergone remission by 3 years of age.6 Second, potential confounders, such as parental atopy, breastfeeding in infancy, treatment methods (such as desensitization techniques), and environmental influences (such as geographic residence), have not been measured. Third, the authors acknowledge that Australia has a high prevalence of allergic disease and this finding may be limited to Western countries. Fourth, because rye grass was the only consistent allergen measured in the study, the actual prevalence of sensitization may be underestimated. Fifth, the authors have not characterized allergic rhinitis because skin prick testing across the ages varied and were not consistent apart from rye grass. Sixth, given that there was subject attendance variation between each study period, the prevalence measurements would vary to a degree. Seventh, information by questionnaire is clearly subject to recall bias. Nevertheless, the long-term prospective nature of this study, high participation rate across the past 4 decades, and good representation of the original cohort at each assessment period support the trends the authors observed in this well-characterized asthma cohort.
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In conclusion, the period of adolescence appeared to be an important phase in this longitudinal asthma cohort whereby eczema prevalence decreased and rhinitis and rye grass sensitization increased. Therefore, attention should be focused on this phase of adolescence to clarify mechanisms to explain the body’s changing response to these disorders. This may lead to treatment options that might modify the incidence and persistence of asthma into adult life. References [1] Downs SH, Marks GB, Sporik R, Belosouva EG, Car NG, Peat JK. Continued increase in the prevalence of asthma and atopy. Arch Dis Child. 2001;84: 20e23. [2] Nina TK, Russell G. Respiratory symptoms and atopy in Aberdeen school children: evidence from two surveys 25 years apart. BMJ. 1992;304:873e875. [3] Peat JK, Salome CM, Woolcock AJ. Longitudinal changes in atopy during a 4 year period: Relation to bronchial hyperresponsiveness and respiratory symptoms in a population sample of Australian schoolchildren. J Allergy Clin Immunol. 1990;85:65e74. [4] Burgess JA, Walters EH, Byrnes GB, et al. Childhood allergic rhinitis predicts asthma incidence and persistence to middle age: a longitudinal study. J Allergy Clin Immunol. 2007;120:863e869. [5] Asher MI, Montefort S, Bjorksten B, et al. Worldwide time trends in the prevalence of symptoms of asthma, allergic rhinoconjunctivitis and eczema in childhood: ISAAC Phases One and Three repeat multi-country cross-sectional surveys. Lancet. 2006;368:733e743.
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