Early Transient Wheeze Research Articles

Phenotypes of childhood wheeze in Japanese children: A group-based trajectory analysis.

Exploring patterns of childhood wheeze may help to clarify the etiology and prognosis of respiratory diseases. The purpose of this study was to classify phenotypes of wheezing in children up to 9years of age in Japan and to evaluate the individual and environmental risk factors for these phenotypes. Wheeze was evaluated at approximately 1-year intervals based on the mothers' recollection of their child's wheezing or whistling in the chest during the preceding 12months. The children were aged 1-9years. In total, 1116 children who had at least five measures of wheezing at all nine time points were used for identifying trajectories. Trajectories were identified with group-based trajectory analysis. A multinomial logit model was built to evaluate the relationships between phenotypes and risk factors. Five typical trajectories were identified. The probability of group membership was 43.7%, 32.2%, 6.2%, 8.6%, and 9.2% for the never/infrequent wheeze, transient early wheeze, school-age-onset wheeze, early-childhood-onset remitting wheeze, and persistent wheeze trajectories, respectively. Infant tobacco exposure increased the odds of membership in the transient early wheeze trajectory compared to the never/infrequent wheeze trajectory. Using the group-based trajectory modeling approach, we identified five trajectories of childhood wheeze development in a Japanese population. The trajectories shown here are based on formal statistical modeling rather than on subjective classification, and an assessment of its precision suggested that the model has high assignment accuracy.

Breastfeeding and Childhood Wheeze: Age-Specific Analyses and Longitudinal Wheezing Phenotypes as Complementary Approaches to the Analysis of Cohort Data

Systematic reviews suggest that breastfeeding is associated with a lower risk of asthma, although marked heterogeneity exists. Using UK Millennium Cohort Study data (n = 10,126 children, born 2000–2002), we examined the association between breastfeeding duration and wheezing in the previous year, first for each age group separately (ages 9 months, 3 years, 5 years, 7 years, and 11 years) and then in terms of a longitudinal wheezing phenotype: “early transient” (wheezing any time up to age 5 years but not thereafter), “late onset” (any time from age 7 years but not beforehand), and “persistent” (any time up to age 5 years and any time from age 7 years). The association between breastfeeding and wheeze varied by age (2-sided P for interaction = 0.0003). For example, breastfeeding for 6–9 months was associated with lower odds of wheezing at ages 9 months, 3 years, and 5 years but less so at ages 7 years and 11 years (adjusted odds ratios = 0.73, 0.78, 0.79, 0.84, 1.06, respectively). There was a strong dose-response relationship for breastfeeding per month and early transient wheeze (adjusted odds ratio for linear trend = 0.961, 95% confidence interval: 0.942, 0.980) but no clear trend for late-onset or persistent wheeze. Our results identified heterogeneity in the association between breastfeeding and wheezing according to age at wheezing and wheezing phenotype.

The Burden and Long-term Respiratory Morbidity Associated with Respiratory Syncytial Virus Infection in Early Childhood.

IntroductionThe REGAL (RSV Evidence—a Geographical Archive of the Literature) series provide a comprehensive review of the published evidence in the field of respiratory syncytial virus (RSV) in Western countries over the last 20 years. The objective of this fifth publication was to determine the long-term respiratory morbidity associated with RSV lower respiratory tract infection (RSV LRTI) in early life.MethodsA systematic review was undertaken for articles published between January 1, 1995 and December 31, 2015. This was supplemented by inclusion of papers published whilst drafting the manuscript. Studies reporting data on the incidence and long-term wheezing and asthma following RSV LRTI in early life were included. Study quality and strength of evidence (SOE) were graded using recognized criteria.ResultsA total of 2337 studies were identified of which 74 were included. Prospective, epidemiologic studies consistently demonstrated that RSV LRTI is a significant risk factor for on-going respiratory morbidity characterized by transient early wheezing and recurrent wheezing and asthma within the first decade of life and possibly into adolescence and adulthood (high SOE). RSV LRTI was also associated with impaired lung function in these children (high SOE). Respiratory morbidity has been shown to result in reduced quality of life and increased healthcare resource use (moderate SOE). The mechanisms through which RSV contributes to wheezing/asthma development are not fully understood, but appear to relate to the viral injury, preexisting abnormal lung function and/or other factors that predispose to wheezing/asthma, including genetic susceptibility, altered immunology, eosinophilia, and associated risk factors such as exposure to environmental tobacco smoke (high SOE).ConclusionThere is growing evidence that RSV LRTI in early childhood is associated with long-term wheezing and asthma and impaired lung function. Future research should aim to fully elucidate the pathophysiological mechanisms through which RSV causes recurrent wheezing/asthma.Electronic supplementary materialThe online version of this article (doi:10.1007/s40121-017-0151-4) contains supplementary material, which is available to authorized users.

Viral Detection and Cytokine Profile in Early Transient Wheeze and Childhood Asthma

Wheeze is a common respiratory symptom in preschool children. Several clinical parameters, including gestational age at birth, parental atopy, and early-life sensitization, are associated with the development of asthma and are used to differentiate between asthma and transient wheeze in early infancy; however, they are only moderately successful. Here, we investigated respiratory viruses and various cytokines/chemokines in transient wheeze cases and established asthma cases.

Patterns in respiratory symptoms up to 7 years old in children from a Spanish birth cohort

Background: Asthma is a heterogeneous syndrome with complex patterns of symptoms whose origin seems to be early in life. Its evolution during childhood is not yet fully understood. Aim: To identify relevant longitudinal patterns of respiratory symptoms until age of 7 years, and the associated factors, in children from a Spanish birth cohort. Methods: Population consisted of 470 children. Symptoms in the last 12 months (wheeze, cough lasting more than 3 weeks, and atopic eczema) were reported by parents at each follow-up (1, 4 and 7 years of age). A clustering analysis method (k-means) was used to identify groups of children with similar patterns of respiratory symptoms over time. Multinomial logistic regression was used to identify the associated factors (history of allergies, individual and socioeconomic factors, and early environmental exposures). Results: Apart from (i) a group of children with low prevalence of symptoms –53.2% of children-, the identified symptomatic patterns were (ii) early transient wheeze –17.4%-; (iii) early transient atopic eczema–14.9%-; and (iv) transient cough at age 4 –14.5%-. Early transient patterns consisted of children with symptoms at age 1 but decreasing later in life. Both patterns of wheeze and cough were related to asthma at age 4. Factors associated with atopic eczema pattern were sex (male), having older siblings at age 1 (protective factor) and sleeping on an old mattress at age 1; for cough pattern, associated factors were living in a big house (>100 m2) and ventilating child’s bedroom more than 2 hours a day at age 1 (protective factor). No factor was significantly related to early transient wheeze pattern. Conclusion: Our study suggests that different patterns of respiratory symptoms could exist during childhood. Early environmental exposures might play a role in their development. However, more studies are needed to validate these patterns and to better identify early modifiable factors for their development.

Risk Factors of Transient Early Wheezing in Infants below 2 years in Fayoum City

The three different phenotypes of wheezing in infants and children are transient early wheezing, non-atopic preschool wheezing and atopic or asthmatic wheezing. Early transient wheezers suffer from wheezing only during the first two years of life due to small airways caliber being more likely to narrow and obstruct. The main phenomena are the absence of personal history and/or family of atopy, so they are born with lung deficiency. Transient early wheezing to represent about 60% among children. There are many risk factors, which predispose to transient early wheezing such as: maternal complications during pregnancy, type of delivery, type of feeding during infancy, overweight infants, passive smoking and day care attendance during infancy. The previous risk factors were studied well in many developed countries but not in our communities including Egypt. Study these risk factors among infants between two months and two years of age and this is the first study done for this common problem among Egyptian children. The study included 160 infants between 2 months and two years, 80 of them were diagnosed as TEW (group 1) and another 80 healthy infants as a control group. Infants were subjected to the following: Detailed history with special emphasize on gestational age -infant gender-infant weight-prenatal and natal history- history of smoking in family- type of delivery -type of feeding. History of recurrent wheezing, need for hospitalization. Full Clinical Examination 3-Investigations: chest x ray and Laboratory tests: Full picture analysis and IgE total enzyme assay. The study revealed that TEW was encountered with large percentage among infants with history of: maternal disease during pregnancy (diabetes, hypertension and urinary tract infection), caesarian section delivery, over weight infants, family history of smoking, artificial feeding, consuming cow milk during first year of life and attendance to daycare during infancy. Overweight is a new risk factor that was observed in our study. Most of the noted risk factors are similar to that reported in studies done in developed countries in addition to overweight infants are associated.

Sex-specific risk factors for childhood wheeze and longitudinal phenotypes of wheeze

Although sexual dimorphism in wheeze and asthma prevalence are well documented, sex-specific risk factors for wheeze and longitudinal wheeze phenotypes have not been well elucidated. By using a large prebirth cohort, this study aimed to identify sex-specific risk factors for wheeze from birth through midchildhood and identify distinct longitudinal wheeze phenotypes and the sex-specific risk factors associated with these phenotypes. Mothers reported child wheeze symptoms over the past year approximately yearly on 9 occasions starting at age 1year. We identified sex-specific predictors of wheeze, wheeze phenotypes, and sex-specific predictors of these phenotypes by using generalized estimating equations, latent class mixed models, and multinomial logistic analysis, respectively. A total of 1623 children had information on wheeze at 1 or more time points. Paternal asthma was a stronger predictor of ever wheezing in boys (odds ratio [OR], 2.15; 95% CI, 1.74-2.66) than in girls (OR, 1.53; 95% CI, 1.19-1.96; P for sex by paternal asthma interaction=.03), whereas being black or Hispanic, birth weight for gestational age z score, and breast-feeding duration had stronger associations among girls. We identified 3 longitudinal wheeze phenotypes: never/infrequent wheeze (74.1%), early transient wheeze (12.7%), and persistent wheeze (13.1%). Compared with never/infrequent wheeze, maternal asthma, infant bronchiolitis, and atopic dermatitis were associated with persistent wheeze in both sexes, but paternal asthma was associated with persistent wheeze in boys only (OR, 4.27; 95% CI, 2.33-7.83; P for sex by paternal asthma interaction=.02), whereas being black or Hispanic was a predictor for girls only. We identified sex-specific predictors of wheeze and longitudinal wheeze patterns, which might have important prognostic value and allow for a more personalized approach to wheeze and asthma treatment.

Childhood Wheeze Phenotypes Show Less Than Expected Growth in FEV1 Across Adolescence

Several “wheeze phenotypes” have been described in early childhood based on age of onset and persistence of wheezing. These include never/infrequent wheeze, early transient wheeze (begins in the first 12 months and resolves by age 3 years), early persistent wheeze (begins in the first 6 months), intermediate-onset wheeze (begins at around 18 months), and late-onset wheeze (begins after age 4 years). What becomes of these children’s lung function over time?An Australian prospective birth cohort of 620 high-allergy-risk children (at least 1 first-degree family member with a history of eczema, asthma, allergic rhinitis, severe food allergy, or any combination of these).Respiratory symptoms and spirometry were recorded at 12 and 18 years. Relationships were assessed comparing wheeze phenotypes and lung function.Deficits in expected growth of lung function, measured by change in forced expiratory volume in 1 second (FEV1) between 12 and 18 years, were found for early persistent (reduced 290 mL; 95% confidence interval [CI], 82–498), intermediate-onset (reduced 210 mL; 95% CI, 62–359), and late-onset wheeze (reduced 255 mL; 95% CI, 69–442). Current asthma risk was increased for all phenotypes except early transient, which was also not associated with lung function deficits at 12 or 18 years.This is the first study to show that persistent childhood wheeze phenotypes were associated with deficits in the growth of FEV1 through to late adolescence. In contrast, early transient wheeze was found to be a benign disorder for adolescent respiratory health.It is troubling that young children with persistent wheeze show marked reduction in lung function/growth as adolescents. This clearly emphasizes the importance of serial spirometry to identify children with declining lung function in whom more aggressive management of their asthma may prevent this. Although it is reassuring that those with early transient wheeze do not show such a decline in lung function, other studies have shown a significant rate of relapse of asthma in adults who had “outgrown” their childhood disease.

Age-specific influence of wheezing phenotypes on pre-adolescent and adolescent health-related quality of life.

Asthma is associated with diminished health-related quality of life (HRQoL). Particularly in adolescence, asthma may be under-diagnosed and undertreated or poorly managed. Therefore, we aimed to determine the association between childhood wheezing phenotypes rather than asthma and adolescent HRQoL in children aged 10-17 yr. We analyzed the data from two prospective population-based cohort studies (n = 604 and n = 1804) conducted in southern Germany with baseline assessments in 2000 and 2006 and follow-ups at frequent intervals. Parent-reported wheeze was categorized into never, early transient, persistent, and late-onset wheeze. We assessed child-reported HRQoL in seven scales using the validated KINDL-R. Multivariate linear regression models were computed. Participants with late-onset wheeze had significantly lower values in all HRQoL scales, but physical well-being compared to never wheezers. Early transient wheeze was negatively associated with three HRQoL scales only (family, school, and total). These effects were confined to the oldest age group (≥13.5 yr) in one study. Persistent wheeze was not associated with HRQoL. In teenagers, late-onset wheezers seem to be particularly vulnerable for impairments in psychosocial aspects of health-related quality of life. They may therefore require particular attention with regard to education about asthma management and potentially family-based psychosocial intervention.

Effects of wheezing in early childhood in the development of allergic rhinitis in later years

BackgroundStudies on the long-term effects of wheezing in infancy have particularly focused on asthma. There isn't adequate information about the effects of wheezing in the development of allergic rhinitis in later years.ObjectiveIn this study, children with wheezing in the first year of life were investigated in terms of allergic rhinitis after five years of age.MethodsThe study consisted of children with early-transient wheezing or persistent wheezing. The study groups were evaluated in terms of allergic rhinitis with physical examination and a questionnaire translated from International Study of Asthma and Allergies in Children (ISAAC) questionnaire after five years of age.ResultsThe study included 50 children; 23 (46%) had early-transient wheezing and 27 (54%) had persistent wheezing. The symptoms of allergic rhinitis were reported in 13 (48%) of children with persistent wheezing but in none of children with early-transient wheezing (p < 0.05). Skin prick tests showed positive results in 4.3% of children with early-transient wheezing and in 48.1% of children with persistent wheezing (p < 0.05).ConclusionPersistent wheezing, but not early transient wheezing seems to be a risk factor in the development of allergic rhinitis in children after five years of age.

The Birth of Mankind

<h3>Background:</h3> Patterns of wheezing during early childhood may indicate differences in aetiology and prognosis of respiratory illnesses. Improved characterisation of wheezing phenotypes could lead to the identification of environmental influences...

Perinatal risk factors for wheezing phenotypes in the first 8 years of life

A novel data-driven approach was used to identify wheezing phenotypes in pre-schoolchildren aged 0-8years, in the Prevention and Incidence of Asthma and Mite Allergy (PIAMA) birth cohort. Five phenotypes were identified: never/infrequent wheeze, transient early wheeze, intermediate onset wheeze, persistent wheeze and late onset wheeze. It is unknown which perinatal risk factors drive development of these phenotypes. The objective of the study was to assess associations of perinatal factors with wheezing phenotypes and to identify possible targets for prevention. In the PIAMA study (n=3963), perinatal factors were collected at 3months, and wheezing was assessed annually until the age of 8years. Associations between perinatal risk factors and the five wheezing phenotypes were assessed using weighted multinomial logistic regression models. Odds ratios were adjusted for confounding variables and calculated with 'never/infrequent wheeze' as reference category. Complete data were available for 2728 children. Risk factors for transient early wheeze (n=455) were male gender, maternal and paternal allergy, low maternal age, high maternal body mass index, short pregnancy duration, smoking during pregnancy, presence of older siblings and day-care attendance. Risk factors for persistent wheeze (n=83) were male gender, maternal and paternal allergy, and not receiving breastfeeding for at least 12weeks. Intermediate onset wheeze (n=98) was associated with a lower birth weight and late onset wheeze (n=45) with maternal allergy. We identified different risk factors for specific childhood wheezing phenotypes. Some of these are modifiable, such as maternal age and body mass index, smoking, day-care attendance and breastfeeding, and may be important targets for prevention programmes.

Early-Life Risk Factors for Childhood Wheeze Phenotypes in a High-Risk Birth Cohort

To define longitudinal childhood wheeze phenotypes and identify their early-life risk factors. Current wheeze was recorded 23 times up to age 7 years in a birth cohort at high risk for allergy (n = 620). Latent class analysis of wheeze responses identified 5 classes. Multinomial logistic regression estimated associations of probability-weighted wheezing classes with early-life factors. All phenotypes were compared with never/infrequent wheezers. Lower respiratory tract infection (LRTI) by 1 year (relative risk [RR], 3.00; 95% CI, 1.58-5.70), childcare by 1 year (RR, 1.51; 95% CI, 1.02-2.22), and higher body mass index (RR, 2.51; 95% CI, 1.09-5.81) were associated with increased risk of early transient wheeze, whereas breastfeeding was protective (RR, 0.54; 95% CI, 0.32-0.90). LRTI (RR, 6.54; 95% CI, 2.55-16.76) and aeroallergen sensitization (RR, 4.95; 95% CI, 1.74-14.02) increased the risk of early persistent wheeze. LRTI (RR, 5.31; 95% CI, 2.71-10.41), eczema (RR, 2.77; 95% CI, 1.78-4.31), aeroallergen sensitization (RR, 5.60; 95% CI, 2.86-10.9), and food sensitization (RR, 2.77; 95% CI, 1.56-4.94) increased the risk of intermediate-onset wheeze, whereas dog exposure at baseline (RR, 0.52; 95% CI, 0.32-0.84) and first-born status (RR, 0.49; 95% CI, 0.32-0.76) were protective. Heavy parental smoking at birth (RR, 3.18; 95% CI, 1.02-9.88) increased the risk of late-onset wheeze, whereas breastfeeding reduced it (RR, 0.34; 95% CI, 0.12-0.96). All wheeze classes except early transient had greater risk of wheeze at age 12 years compared with never/infrequent wheezers. We found distinct early-life risk factor profiles for each wheeze phenotype. These findings provide insight into possible wheeze mechanisms and have implications for identifying preventive strategies and addressing clinical management of early-life wheeze.

Wheezing in preschool children

Wheezing is a common condition in pediatric practice, it can be defined as a musical sound, high-pitched and continuous, emitting from the chest during breath exhalation.Although almost 50% of children experiences wheeze in the first 6years of life, only 40% of them will report continued wheezing symptoms after childhood. The classification of wheeze in preschool children is more difficult compared to school aged children. It is based on the onset and duration of symptoms and divided children in three categories: transient early wheezing, non-atopic wheezing and atopic wheezing/asthma.History and physical examination, skin prick test, exhaled nitric oxide, lung function test are the parameter to evaluate children with wheezing.The aim of management of wheezing is to finalize the control of symptoms, reduce exacerbations and improve the quality of life. All guidelines underline the complexity in making a diagnosis of asthma under five years and the need to identify phenotypes that may help paediatricians in the therapeutic choices.

Joint modeling of parentally reported and physician-confirmed wheeze identifies children with persistent troublesome wheezing

Previous studies have suggested the presence of different childhood wheeze phenotypes through statistical modeling based on parentally reported wheezing. We sought to investigate whether joint modeling of observations from both medical records and parental reports helps to more accurately define wheezing disorders during childhood and whether incorporating information from medical records better characterizes severity. In a population-based birth cohort (n = 1184), we analyzed data from 2 sources (parentally reported current wheeze at 4 follow-ups and physician-confirmed wheeze from medical records in each year from birth to age 8 years) to determine classes of children who differ in wheeze trajectories. We tested the validity of these classes by examining their relationships with objective outcomes (lung function, airway hyperreactivity, and atopy), asthma medication, and severe exacerbations. Longitudinal latent class modeling identified a 5-class model that best described the data. We assigned classes as follows: no wheezing (53.3%), transient early wheeze (13.7%), late-onset wheeze (16.7%), persistent controlled wheeze (13.1%), and persistent troublesome wheeze (PTW; 3.2%). Longitudinal trajectories of atopy and lung function differed significantly between classes. Patients in the PTW class had diminished lung function and more hyperreactive airways compared with all other classes. We observed striking differences in exacerbations, hospitalizations, and unscheduled visits, all of which were markedly higher in patients in the PTW class compared with those in the other classes. For example, the risk of exacerbation was much higher in patients in the PTW class compared with patients with persistent controlled wheeze (odds ratio [OR], 3.58; 95% CI, 1.27-10.09), late-onset wheeze (OR, 15.92; 95% CI, 5.61-45.15), and transient early wheeze (OR, 12.24; 95% CI, 4.28-35.03). We identified a novel group of children with persistent troublesome wheezing, who have markedly different outcomes compared with persistent wheezers with controlled disease.

Transient early wheeze and lung function in early childhood associated with chronic obstructive pulmonary disease genes

It has been hypothesized that a disturbed early lung development underlies the susceptibility to chronic obstructive pulmonary disease (COPD). Little is known about whether subjects genetically predisposed to COPD show their first symptoms or reduced lung function in childhood. We investigated whether replicated genes for COPD associate with transient early wheeze (TEW) and lung function levels in 6- to 8-year-old children and whether cigarette smoke exposure in utero and after birth (environmental tobacco smoke [ETS]) modifies these effects. The association of COPD-related genotypes of 20 single nucleotide polymorphisms in 15 genes with TEW, FEV1, forced vital capacity (FVC), and FEV1/FVC ratio was studied in the Prevention and Incidence of Asthma and Mite Allergy (PIAMA) birth cohort (n= 1996) and replicated in the Child, parents and health: lifestyle and genetic constitution (KOALA) and Avon Longitudinal Study of Parents and Children (ALSPAC) cohorts. AGER showed replicated association with FEV1/FVC ratio. TNS1 associated with more TEW in PIAMA and lower FEV1 in ALSPAC. TNS1 interacted with ETS in PIAMA, showing lower FEV1 in exposed children. HHIP rs1828591 interacted with cigarette smoke exposure in utero in PIAMA and with ETS in ALSPAC, with lower lung function in nonexposed children. SERPINE2, FAM13A, and MMP12 associated with higher FEV1 and FVC, and SERPINE2, HHIP, and TGFB1 interacted with cigarette smoke exposure in utero in PIAMA only, showing adverse effects of exposure on FEV1 being limited to children with genotypes conferring the lowest risk of COPD. Our findings indicate relevant involvement of at least 3 COPD genes in lung development and lung growth by demonstrating associations pointing toward reduced airway caliber in early childhood. Furthermore, our results suggest that COPD genes are involved in the infant's lung response to smoke exposure in utero and in early life.

Cord serum 25-hydroxyvitamin D and risk of early childhood transient wheezing and atopic dermatitis

There is increasing evidence of the effect of maternal vitamin D intake during pregnancy on the risk of asthma and allergic outcomes in offspring. However, studies on the relationship between cord levels of 25-hydroxyvitamin D (25[OH]D) and asthma and allergic diseases are very few. Our aim was to investigate the associations between cord serum 25(OH)D levels and asthma, wheezing, allergic rhinitis, and atopic dermatitis in the offspring from birth to 5 years. Cord blood samples were collected at birth and analyzed for 25(OH)D levels in 239 newborns from the Etude des Déterminants pré et post natals du développement et de la santé de l'Enfant (EDEN) birth cohort. The children were followed up until age 5 years by using International Study of Asthma and Allergies in Childhood-based symptom questionnaires. The median cord serum level of 25(OH)D was 17.8 ng/mL (interquartile range, 15.1 ng/mL). By using multivariable-adjusted logistic regression models, a significant inverse association was observed between cord serum 25(OH)D levels and risk of transient early wheezing and early- and late-onset atopic dermatitis, as well as atopic dermatitis, by the ages of 1, 2, 3, and 5 years. We found no association between cord serum 25(OH)D levels and asthma and allergic rhinitis at age 5 years. Cord serum 25(OH)D levels were inversely associated with the risk of transient early wheezing and atopic dermatitis by the age of 5 years, but no association was found with asthma and allergic rhinitis.

Forkhead box protein 3 (FOXP3) hypermethylation is associated with diesel exhaust exposure and risk for childhood asthma

Kelly J. Brunst, Ph.D.1,2,†, Yuet-Kin Leung, Ph.D.2,3, Patrick H. Ryan, Ph.D.1,2,4, Gurjit K. Khurana Hershey, M.D., Ph.D.5, Linda Levin, Ph.D.1,2, Hong Ji, Ph.D.5, Grace K. LeMasters, Ph.D.1, and Shuk-Mei Ho, Ph.D.2,3,6 1Division of Epidemiology and Biostatistics, University of Cincinnati College of Medicine, 3223 Eden Avenue, Kettering Building, Cincinnati, OH 2Center for Environmental Genetics, University of Cincinnati College of Medicine, 3223 Eden Avenue, Kettering Building, Cincinnati, OH 3Division of Environmental Genetics and Molecular Toxicology, Department of Environmental Health, University of Cincinnati College of Medicine, 3223 Eden Avenue, Kettering Building, Cincinnati, OH 4Division of Biostatistics and Epidemiology, Cincinnati Children’s Hospital Medical Center, 3333 Burnet Avenue, MLC 7037, Cincinnati, OH 5Division of Asthma Research, Cincinnati Children’s Hospital Medical Center, 3333 Burnet Avenue, MLC 7037, Cincinnati, OH 6Cincinnati Veteran Affairs Medical Center, Merit Scholar, 3200 Vine Street, Cincinnati, OH

Associations of Different Phenotypes of Wheezing Illness in Early Childhood with Environmental Variables Implicated in the Aetiology of Asthma

RationaleAsthma is a complex heterogeneous disease that has increased in prevalence in many industrialised countries. However, the causes of asthma inception remain elusive. Consideration of sub-phenotypes of wheezing may reveal important clues to aetiological risk factors.MethodsLongitudinal phenotypes capturing population heterogeneity in wheezing reports from birth to 7 years were derived using latent class analysis in the Avon Longitudinal Study of Parents and Children (ALSPAC). Probability of class membership was used to examine the association between five wheezing phenotypes (transient early, prolonged early, intermediate-onset, late-onset, persistent) and early life risk factors for asthma.ResultsPhenotypes had similar patterns and strengths of associations with early environmental factors. Comparing transient early with prolonged early wheezing showed a similar pattern of association with most exposure variables considered in terms of the direction of the effect estimates but with prolonged early wheezing tending to have stronger associations than transient early wheezing except for parity and day care attendance.ConclusionsAssociations with early life risk factors suggested that prolonged early wheeze might be a severe form of transient early wheezing. Although differences were found in the associations of early life risk factors with individual phenotypes, these did not point to novel aetiological pathways. Persistent wheezing phenotype has features suggesting overlap of early and late-onset phenotypes.

Does eczema in infancy cause hay fever, asthma, or both in childhood? Insights from a novel regression model of sibling data

The atopic march hypothesis proposes that eczema precedes the development of asthma and allergic rhinitis. We sought to assess the evidence for a causal effect of infantile eczema on childhood hay fever, asthma, or both. We used parental reports on infantile eczema and childhood asthma and hay fever for 3778 pairs of 7-year-olds matched to their sibling closest in age within 2 years from the Tasmanian Longitudinal Health Study. We analyzed paired sibling data using a logistic regression model that allowed inference about a causal effect of a familial predictor on a child's outcome by examining the change in association with their cosibling's predictor after adjusting for their own predictor status. Siblings were concordant for infantile eczema (tetrachoric correlation, 0.40). For having both hay fever and asthma by age 7 years, the association with cosibling's eczema was an odds ratio (OR) of 1.98 (95% CI, 1.37-2.86), which reduced after adjusting for own eczema to an OR of 1.65 (95% CI, 1.17-2.34). For having hay fever only, the association with cosibling's eczema was an OR of 1.68 (95% CI, 1.22-2.31) before and an OR of 1.59 (95% CI, 1.19-2.14) after adjusting for own eczema. There was no association between having asthma only and cosibling's eczema (OR, 1.00; 95% CI, 0.77-1.30). Eczema in infancy might have a causal effect on hay fever in children with and perhaps without asthma. The association of infantile eczema on asthma in children without hay fever, which might be early transient wheeze, is unlikely to be causal or familial. These findings have implications for hay fever prevention.