Transient Wheeze Research Articles

Maternal Complications and Procedures in Pregnancy and at Birth and Wheezing Phenotypes in Children

There is increasing interest in the potential influence of fetal and early life conditions on childhood wheezing. To investigate the associations between maternal complications and procedures in pregnancy and at birth and the risk of various wheezing phenotypes in young children. We studied 15,609 children, aged 6-7 yr, enrolled in a population-based study. Standardized questionnaires were completed by the children's mothers. Of the children, 9.5% (1,478) had transient early wheezing, 5.4% (884) had persistent wheezing, and 6.1% (948) had late-onset wheezing. Maternal hypertension or preeclampsia was associated with an increased risk of all three wheezing phenotypes (for transient early wheezing: odds ratio [OR], 1.40; 95% confidence interval [95% CI], 1.08-1.82; for persistent wheezing: OR, 1.59; 95% CI, 1.15-2.19; and for late-onset wheezing: OR, 1.47; 95% CI, 1.06-2.01). Use of antibiotics for urinary tract infections was associated with transient early wheezing (OR, 1.52; 95% CI, 1.16-2.00), whereas antibiotic administration at delivery was associated with both transient early wheezing (OR, 1.21; 95% CI, 1.01-1.46) and persistent wheezing (OR, 1.39; 95% CI, 1.10-1.75). Children who had a mother with diabetes were also more likely to have persistent wheezing (OR, 1.72; 95% CI, 0.99-3.00). Neither amniocentesis/chorionic villus sampling, nor weight gain in pregnancy, nor cesarean section was associated with the subsequent development of wheezing. Maternal asthma or atopy was not an effect modifier of the associations found. Some maternal complications during pregnancy and at delivery may increase the risk of developing different phenotypes of wheezing in childhood.

Wheeze Phenotypes and Lung Function in Preschool Children

Purpose of the Study. To determine the relationship between wheeze phenotypes in childhood and lung function at age 3 and 5 years and determine if lung function at 3 years of age predicts the development or persistence of wheeze. Study Population. A population-based cohort of 874 children from the Manchester Asthma and Allergy Study. Subjects were recruited prenatally and followed up at 3 and 5 years of age. Methods. Subjects were assigned to categories on the basis of parental report of wheezing: “no wheezing” was defined as no wheezing by age 5; “transient early wheezing” was defined as wheezing before age 3 but none in the year before the 5-year follow-up; “late-onset wheezing” was defined as no wheezing before age 3 but wheezing in the 12 months before the 5-year follow-up; and “persistent wheezing” was defined as wheezing before age 3 and in the year before the 5-year follow-up. Specific airway resistance (sRAW) was measured at age 3 and 5 by body plethysmography when subjects were symptom-free. Postbronchodilator lung function was measured as sRAW after albuterol inhalation. Results. The 530 (60.6%) subjects successfully performing sRAW at age 3 were distributed as: 248 never wheezed, 115 had transient early wheeze, 22 had late-onset wheezing, and 78 had persistent wheezing. The 730 children successfully performing sRAW at 5 years old were distributed as: 384 never wheezed, 162 had transient early wheeze, 40 had late-onset wheeze, 104 had persistent wheeze, and 40 were not classifiable. At 3 years of age, the only significant differences in sRAW between groups was an increased resistance in those with persistent wheeze compared with children with late-onset wheeze (P = .04) and those who never wheezed (P < .001). At 5 years of age, sRAW was elevated in children with persistent wheeze compared with those with transient early wheeze (P = .02) and those who never wheezed (P < .001). Also, sRAW was significantly higher in those with transient-early wheezing compared with those who never wheezed (P = .01), but there was no significant difference between those who never wheezed and those with late-onset wheezing (P = .43). Among the subgroup of children who had wheezed by age 3, the risk of persistent wheeze increased markedly with increasing sRAW values. Conclusions. Children with persistent wheeze have reduced lung function at 3 and 5 years compared with other wheeze phenotypes. In children who wheezed during the first 3 years of life, reduced lung function at age 3 predicted persistent wheezing. However, reduced lung function at age 3 did not predict late-onset wheeze in those who had not wheezed previously. Reviewer Comments. It would be useful to be able to predict whether wheezing early in life will be transient or persistent. This study augments the findings of the similarly sized, longitudinal, Tucson Children’s Respiratory Study by suggesting that (1) poor lung function at age 3 is a predictor of persistent symptoms in those with a history of early wheezing, but for individuals the measurement has limited predictive value; (2) children with transient early wheezing have increased airflow resistance at age 5 compared with those who never wheezed; and (3) those with persistent wheeze and transient early wheeze both have airflow obstruction compared with the group who never wheezed. At age 5, the group with persistent wheeze also had lower postbronchodilator lung function than the group with no wheeze, indicating that factors other than smooth muscle contraction are present early in life. Additional studies are needed to determine the factors contributing to poor lung function early in life and to identify measures that would predict persistent wheezing in individuals.

The many faces of the hygiene hypothesis

About 15 years have gone by since Strachan first proposed the idea that infections and unhygienic contact might confer protection against the development of allergic illnesses. The so-called hygiene hypothesis has ever since undergone numerous more or less subtle modifications by various researchers in the fields of epidemiology, clinical science, and immunology. Three major tracts have developed exploring the role of overt viral and bacterial infections, the significance of environmental exposure to microbial compounds, and the effect of both on underlying responses of the innate and adaptive immunity. To date, a truly unifying concept has not yet emerged, but various pieces of a complex interplay between immune responses of the host, characteristics of the invading microorganism, the level and variety of the environmental exposure, and the interactions between a genetic background and a range of exposures becomes apparent. These influences are discussed as determinants for a number of complex allergic illnesses in this review, while we attempt to pay attention to the importance of different phenotypes, namely of the asthma syndrome. Even if today practical implications cannot directly be deduced from these findings, there is great potential for the development of novel preventive and therapeutic strategies in the future.

Does early indoor microbial exposure reduce the risk of asthma? The Prevention and Incidence of Asthma and Mite Allergy birth cohort study

Exposure to microbial agents might inhibit the development of atopy and asthma. We measured the association between microbial exposure assessed at 3 months and the development of atopic sensitization and doctor-diagnosed (DD) asthma and wheeze in the first 4 years in a birth cohort study of children with atopic mothers. Endotoxin, fungal (1-->3)-beta-D-glucans, extracellular polysaccharides from the genera Penicillium and Aspergillus (EPS-Pen/Asp), and dust on living room floors were measured at 3 months of age. Serum IgE levels against common allergens were determined at 1 and 4 years, and questionnaire information about respiratory morbidity was collected yearly. Microbial levels in mattresses were low and not associated with serum IgE levels, DD asthma, and wheeze. Floor levels of biocontaminants and dust, on the other hand, were inversely associated with DD asthma, being most pronounced for endotoxin (odds ratio [OR], 0.40; 95% CI, 0.21-0.77) and EPS-Pen/Asp (OR, 0.42; 95% CI, 0.18-0.99). Mutual adjustment for other exposures did not significantly alter the results for endotoxin and only moderately affected the results for EPS-Pen/Asp. Persistent wheeze was also consistently less common in the high-exposure group, being significant only for EPS-Pen/Asp (OR, 0.37; 95% CI, 0.15-0.96). Transient wheeze and wheeze in the past 12 months were also reduced, but effects were smaller and not significant. Relationships with serum-specific IgE levels, which could only be assessed in 41% at age 4 years, were less pronounced and statistically significant only for EPS-Pen/Asp. Early exposure to common microbial contaminants, including fungal agents, might protect against asthma. Microbial exposure in early life might protect against asthma and might constitute a novel target for prevention.

Characteristics of Early Transient, Persistent, and Late Onset Wheezers at 9 to 11 Years of Age

Study objective. To investigate the early determinants and characteristics of different phenotypes of wheeze in children on the basis of questionnaire data, lung function, and prick tests. Design. Cross-sectional survey. Setting. Rome and Fiumicino municipalities in Lazio region, Italy, within the ISAAC phase II project. Subjects. Sample of 2107 9–11 year old schoolchildren (response rate 83.5%). Results. We divided children into four mutually exclusive groups according to onset of wheeze: 154 early transient (birth to age 2), 51 persistent (birth to age 2 and current), 66 late onset (current only), and 1,446 control subjects (no early or current wheeze). Logistic regression models have shown that a family history of asthma and allergies is strongly associated with persistent and late onset wheezing; exposure to parental smoking—both during pregnancy and during the child's first year of life—is related to persistent wheezing; all children with wheezing show a significantly greater risk to have current respiratory symptoms other than wheeze compared with control subjects; current allergic rhinoconjunctivitis symptoms and atopy are related with both persistent and late onset wheeze. Multiple linear regression models show that forced expiratory rates at 25% to 75% of vital capacity (FEF25−75) and the ratio between forced expiratory volume in 1 second and forced vital capacity (FEV1/FVC) are significantly lower both in early transient (−305 mL/s, −1.7%) and persistent (−298 mL/s, −3.2%) wheezers; FEV1/FVC is significantly reduced in late onset wheezers too (−2.0%). Conclusions. The strength of the association of family history and exposure to parental smoking varies with the three wheezing phenotypes. Moreover, early, persistent and late onset wheezers have different clinical characteristics in terms of their respiratory health and atopic status.

Paediatric basis of adult lung disease

Most lung disease throughout life is programmed in utero or early post-natal life. Factors in the fetal environment such as maternal smoking and diet can lead to reduced lung function, immunological modification or symptoms from birth. There are clear genetic components documented for cystic fibrosis, alpha1 anti-trypsin deficiency and asthma. In early life, the outcomes for those predisposed to asthma or allergy appear to be dependent on the relative timing of exposure to infective agents, allergens or helminths. Abnormal airway structure is present in both transient and persistent wheezers. New drugs and environmental manipulations will need to be developed with an understanding of the mechanisms associated with this early programming.

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Factors predicting the persistence of asthma insights from the Tucson children’s respiratory study

The Tucson Children’s Respiratory Study (TCRS) is a longitudinal, epidemiology study of respiratory health, which enrolled a birth cohort of over 1200 children from 1980 to 1984. Over 800 of these children were still being followed at adolescence allowing the characterization of several distinct wheezing phenotypes throughout childhood, as well as, those risk factors associated with the development of asthma and its persistence. Evaluating the persistence of asthma is a complex issue. There are several distinct wheezing phenotypes in childhood, which vary in prevalence and course with age. The challenge here is that the phenotypes of wheezing illness change with age; i.e. in infancy most children with wheezing illnesses are transient wheezers who will cease wheezing by age six. In contrast, by age six most children with wheeze have either persisted since infancy without apparent remission or have late onset wheeze. Both of these groups have increased rates of atopy representing dysregulated immune systems. Although its prevalence decreases substantively by early adolescence, non-atopic wheeze continues in a relevant proportion of school age children. Further, although the majority of adolescents with asthma have developed wheeze by age six, there are some who first present with asthma after this age. Thus, as children age, the meaning of wheezing transitions from most likely not being asthma in the first 3 years to most likely being asthma by late adolescence. This article will review the progression of wheezing from infancy through early adolescence and will address both changes in phenotypes as well as risk factors for both persistent and incident asthma in childhood. L’étude respiratoire pédiatrique de Tucson est une étude épidémiologique longitudinale de santé respiratoire ; une cohorte de 1200 enfants a été enrôlée depuis naissance, entre les années 1980 à 1984. Huit cents de ces enfants sont toujours suivis à l’adolescence, ce qui permet de caractériser plusieurs phénotypes distincts de sifflements et aussi de mettre en évidence les facteurs de risques associés au développement et à la persistance de l’asthme. Evaluer la persistance de l’asthme est d’une réelle complexité. Il existe chez l’enfant plusieurs phénotypes de sifflements dont la prévalence et l’évolution varient avec l’age. Le « challenge » est que les phénotypes de sifflements changent avec l’âge. La plupart des nourrissons siffleurs sont des siffleurs transitoires qui s’arrêtent de siffler à six ans. En revanche, à l’âge de six ans, la plupart des enfants siffleurs soit n’ont jamais arrêté vraiment de siffler soit ont commencé à siffler tardivement. Dans ces deux groupes, la fréquence de l’atopie est élevée, témoin d’une dysrégulation immunitaire. Les sifflements non atopiques, même si leur fréquence diminue notablement en préadolescence, persistent chez une proportion significative d’enfants d’âge scolaire. De plus, même si la majorité des adolescents asthmatique avait débuté leur asthme avant l’age de six ans, chez certains, l’asthme n’apparaît qu’après cet age. Ainsi, au fur et à mesure que les enfants vieillissent, la signification des sifflements (wheezing) se transforme : asthme fort peu probable jusqu’à trois ans mais asthme fort probable en fin d’adolescence. Cet article décrit la progression des sifflements depuis le nourrisson jusqu’au début de l’adolescence, les changements des phénotypes ainsi que les facteurs de risque de l’asthme persistant et de l’asthme épisodique.

THE ASSOCIATION BETWEEN HLA-DR, -DQ GENES AND SUSCEPTIBILITY TO ATOPY IN A BIRTH COHORT

ISEE-202 Introduction: Atopic disease in early childhood plays a major role in the development of asthma in childhood or adolescence. Different human leukocyte antigen (HLA) class II alleles have been associated with the development of atopic asthma and responsiveness of allergen exposure. HLA class II molecules were found in neonates’ immune system. However, the relationship between the atopic disease in early childhood and HLA-DR and -DQ genes remains unclear. Aim: Our aim is to determine the association between HLA-DR and -DQ genes and susceptibility to atopy in a birth cohort at one year follow-up. Methods: Four private maternity hospitals were randomly selected to participate and recruit pairs of mothers and neonates. A questionnaire was administered to collect demographic data, home environment, family disease histories, and information about atopic symptoms including early-onset transient wheezing, atopic dermatitis, and eczema, diagnosed by paediatricians. The questionnaire was completed by neonates’ parents when neonates were followed up to the age of 1 year by telephone interview. The levels of cord blood IgE (cIgE) and maternal total IgE (sIgE) and allergen-specific IgE were determined by the Pharmacia UniCAP IgE assay test system. HLA-DR and -DQ alleles were typed using the Dynal AllSet+™ “low resolution” SSP kit. Results: Between July 2001 and May 2003, 187 mother and neonate pairs participated in this study. A total of 184 neonates completed the HLA-DR and -DQ genotyping. The frequencies of HLA-DR and -DQ genes, maternal sensitization, sIgE > 100 IU/ml, and cIgE ≥ 0.35 IU/ml were not different between the four areas. No association was found between cIgE and HLA-DR and -DQ genes or atopic symptoms. Physician diagnosed atopic symptoms were associated with the HLA-DQB1*02 allele (X2= 10.38, p<0.0013). After adjusting for possible potential risk factors, the sIgE > 100 IU/ml (Odds Ratio (OR) =5.01, 95% ci= [1.22, 27.14]), and HLA-DQB1*02 (OR = 8.09, 95% CI= [1.91, 36.74]) were risk factors for atopic symptoms in children at one year follow-up. Conclusion: Although, no allergen-specific IgE data were found in infants, we suggest that HLA-DQB1*02 and maternal atopy are important risk factors for atopic symptoms in early stage of childhood. Elucidating this interaction at the molecular level may allow for more targeted treatment and prevention of atopic diseases.

Outcome of Asthma and Wheezing in the First 6 Years of Life

The effect of early life wheezing on respiratory function and continued symptoms through adolescence has not been fully described. Using data from a population-based birth cohort in Tucson, Arizona, we previously described four phenotypes based on the occurrence of wheezing lower respiratory illnesses before age 3 yr and active wheeze at age 6 yr: never wheezers (n = 425), transient early wheezers (n = 164), persistent wheezers (n = 113), and late-onset wheezers (n = 124). We sought to determine the prognosis for these phenotypes, with reference to lung function and symptoms, through adolescence. Current wheeze was assessed by questionnaire, lung function was measured by conventional spirometry, and atopy was determined by skin prick tests. The prevalence of atopy and wheeze by age 16 yr was similar for never and transient wheezers and for persistent and late-onset wheezers. Both transient early, and persistent wheezers had significantly lower FEF(25-75) (-259 ml/s, p < 0.001, and -260 ml/s, p = 0.001, respectively), FEV1 (-75 ml, p = 0.02, and -87 ml, p = 0.03, respectively), and FEV1:FVC ratio (-1.9%, p = 0.002, and -2.5%, p = 0.001, respectively) through age 16 yr compared with never wheezers. Late-onset wheezers had levels of lung function similar to those of never wheezers through age 16 yr. There was no significant change in lung function among subjects with any of the four phenotypes, relative to their peers, from age 6 to 16 yr. Patterns of wheezing prevalence and levels of lung function are established by age 6 yr and do not appear to change significantly by age 16 yr in children who start having asthma-like symptoms during the preschool years.

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Some evidence suggests that early-life respiratory events might play a significant role in respiratory health throughout life. There have been retrospective classifications of wheezing phenotypes in childhood, such as (1) transient early wheezing, (2) late-onset wheezing, (3) persistent wheezing, and (4) never wheezed. In this prospective, population-based, birth cohort study in the United Kingdom, the parentally reported patterns of childhood wheezing obtained when the children were 3 and 5 years of age were compared with pulmonary function in these children as assessed by airways resistance measurements.

Are influences during pregnancy associated with wheezing phenotypes during the first decade of life?

Recently, attention has focused on possible early life origins for asthma. We sought to identify whether factors present during pregnancy were associated with development of childhood wheezing phenotypes. A whole population birth cohort (n=1456) on the Isle of Wight, UK, was followed through to age 10 y. Where possible, information regarding environmental exposures and events during pregnancy was obtained from the maternity records (n=1238). Children were seen at ages 1, 2, 4 and 10 y, and wheezing symptoms were used to define wheezing phenotypes in the first decade (n=1034). Risk of early-onsetpersistent wheeze (onset in the first 4 y, still present at age 10) was increased by environmental tobacco smoke exposure in pregnancy (OR=2.44; 95% CI: 1.37-4.34) plus maternal asthma (3.57; 1.84-6.94), but reduced by cat ownership (0.30; 0.13-0.62). Early transient wheeze (onset in the first 4 y, but not present at age 10) was increased by environmental tobacco smoke exposure (1.58; 1.02-2.45), male gender (1.68; 1.09-2.60) and low birthweight (3.65; 1.27-10.52). No environmental factors in pregnancy were associated with late-onset persistent wheeze (onset after age 4 y, still present at 10 y). In addition to genetics, maternal exposures during pregnancy show association with childhood and especially early-life wheezing phenotypes.

Does bronchiolitis caused by RSV predispose to atopic asthma?

Based on results from the Tucson Children's Respiratory Study, three different forms of wheezing in children have been proposed: transient infant wheezers, non-atopic wheezers, and atopic wheezers (i.e. children with atopic asthma with IgE antibodies to environmental allergens). All controlled studies of children with RSV bronchiolitis in infancy have revealed that wheezing can continue for varying lengths of time after the infection has subsided. The pathophysiology of this disorder remains to be clarified. Is this wheezing a transient and benign condition, or is it non-atopic, in which case the long-term prognosis is good, or is it a marker for atopic asthma? We have followed prospectively 47 children hospitalised with RSV bronchiolitis and 93 non-bronchiolitis matched controls. The results of follow-up examinations at age 3 and 7 years showed that the incidence of asthma—in children with or without IgE antibodies—was significantly increased in the RSV bronchiolitis group compared to the control group. We observed similar results in a recent follow-up study of these same children at age 13. Our results suggest that infants with RSV bronchiolitis severe enough to cause hospitalisation are at risk for atopic asthma at age 13.

Development of atopy and wheezing symptoms in relation to heredity and early pet keeping in a Swedish birth cohort.

The role of pet keeping during infancy for the development of allergy and asthma is still controversial. The objective of this population-based birth cohort study was to assess the development of atopy and different wheezing phenotypes during the first 4 yr of life in relation to heredity and early pet keeping. The cohort comprised all 1228 infants living in a Swedish county who were born over a 1-yr period. The parents replied to repeated questionnaires and 817 of the children were skin prick tested both at 1 and 4 yr. Cat keeping during the first year of life was associated with an increased risk of a positive skin prick test to cat at 1 yr of age [odds ratio (OR) 2.2, 95% confidence interval (CI) 0.9-5.6], but neither with sensitivity nor clinical symptoms of allergy at 4 yr. Dog keeping during the first year of life was associated with an increased risk of early-onset transient wheezing, but only in children with parental asthma (adjusted OR 4.3, 95% CI 1.5-12.1). In contrast, early dog keeping had an inverse association with sensitivity to pollen allergen at 4 yr (adjusted OR 0.3, 95% CI 0.1-0.9) and late-onset wheezing (adjusted OR 0.4, 95% CI 0.2-1.0). Thus, pet keeping during the first year of life was not associated with an increased risk of atopy at 4 yr, although a positive SPT to cat was more common at 1 yr. Our findings may even suggest that dog keeping during the first year of life might provide some protection from pollen allergy and late-onset wheezing and increase the risk of early-onset transient wheezing in children with heredity for asthma.

Influence of male sex and parental allergic disease on childhood wheezing: role of interactions.

Boys have been reported to be more susceptible to childhood wheezing, whereas girls are more susceptible later in life. This difference might be related to both genetic and environmental factors. To investigate the influence of male sex and parental allergic disease on the development of childhood wheezing. Infants (n=4089) born in Stockholm were recruited in a prospective study, BAMSE. Data on parental allergic diseases were obtained from questionnaires answered at the children's birth and on symptoms of wheezing at 1, 2 and 4 years of age. Sensitization to inhalant allergens and lung function was investigated at the age of 4 years. Children were classified as having recurrent, transient (n=266), early-onset persistent (n=319) and late-onset wheezing (n=195). Boys were over-represented in all groups of wheezing (odds ratio, OR=1.4-1.5) and both maternal and paternal allergic disease was of importance for the wheezing outcomes. A dominating influence from maternal allergic disease was only seen in children with persistent wheezing. An interaction exceeding additivity was found between male sex and parental allergic disease, particularly in children with persistent wheezing (OR=2.9 and 95% confidence interval, CI 95% 2.1-4.0 for boys with any parental history vs. OR=1.4, CI 95% 1.0-2.1 for girls). Interaction between male sex and parental allergic disease was also observed in children who wheezed at the age of 4 years and were sensitized to inhalant allergens. Our data suggest an interaction between male sex and parental allergic disease in childhood wheezing, which may represent a sex-specific genetic influence.

Symptoms, lung function, and beta2-adrenoceptor polymorphisms in a birth cohort followed for 10 years.

As little is known about the natural history of bronchial responsiveness and the development of wheezing symptoms in early childhood, a cohort of children at risk of allergy, whose lung function and bronchial responsiveness had been measured in the neonatal period, was followed prospectively for 10 (SD, 0.8) years in order to determine the role of neonatal measurements on wheezing history and later lung function. A potential role for beta-2 adrenoceptor (beta2AR) polymorphisms in these relationships was also sought as a secondary objective. Of the original 73 children, wheezing history was available in 65 (89%), and 49 (67%) attended the laboratory for physiological measurements and genotyping of beta2AR. Wheezing was categorized as occurring 1) only before the fourth birthday, 2) after the fourth birthday, or 3) never. No relation was seen between neonatal and later lung function. However, neonatal bronchial responsiveness predicted subsequent FEV1 (P = 0.03). Increased neonatal bronchial responsiveness was associated with transient wheeze <4 years but not with later wheeze. Neonatal V'maxFRC was reduced in those possessing Gln27 or Arg16 alleles, but there was no effect of beta2AR polymorphisms on FEV1 at 10 years. Wheeze after 4 years of age was typical of classical asthma, as it was strongly related to atopy and bronchial responsiveness at age 10. In conclusion, we confirmed the association of neonatal bronchial responsiveness with both early wheezing and later lung function. We also showed an influence of polymorphisms at both aa16 and aa27 on neonatal lung function. Wheezing beyond 4 years, typical of classical asthma, was unrelated to early measurements of lung function or bronchial responsiveness.

Asthma phenotypes in childhood: lessons from an epidemiological approach.

Asthma is a heterogenous disease with variable signs and symptoms among patients. It also presents significant individual variability over time. Recently, some important population-based studies that followed children from birth or from early childhood into adulthood have shed new light on how we understand this syndrome. Three phenotypes have been identified in children with asthma: transient wheezing, non-atopic wheezing of the toddler and pre-school-aged child and IgE-mediated wheezing. Transient wheezing is associated with symptoms that are limited to the first 3-5 years of life, decreased lung function, maternal smoking during pregnancy and exposure to other siblings or children at daycare centres. There is no association between transient wheezing and family history of asthma or allergic sensitisation. Children wheezing with respiratory syncytial virus in the first years of life are more likely to be wheezing up to 13 years of age; this is independent of atopy (non-atopic wheezers) and is not related to atopic sensitisation. Wheezing associated with evidence of allergic sensitisation has been identified as the 'classic' asthma phenotype. Early allergic sensitisation is a major risk factor for persistent asthma.

The introduction of solids in relation to asthma and eczema

Background: Despite scarce scientific evidence, current feeding guidelines recommend delayed introduction of solids for the prevention of asthma and allergy. Aims: To explore whether late introduction of solids is protective...

Childhood asthma.

The prevalence of asthma and wheezing illness in children has increased substantially over recent decades and places a large burden on health care resources. Despite increasing evidence that both genetic and environmental factors have significant effects on airway development and function in early life, our understanding of the natural history of the disease is limited. Several phenotypes of wheeze have been described and many risk factors identified for the development of asthma. A thorough knowledge of early life lung physiology will enable us to identify children at risk for developing persistent disease. The development of objective outcome measures that can be applied in early life will aid in distinguishing between children with transient early wheeze and those who will progress to persistent disease, enabling effective, targeted therapy.

Early-life environmental risk factors for asthma: findings from the Children's Health Study.

Early-life experiences and environmental exposures have been associated with childhood asthma. To investigate further whether the timing of such experiences and exposures is associated with the occurrence of asthma by 5 years of age, we conducted a prevalence case-control study nested within the Children's Health Study, a population-based study of > 4,000 school-aged children in 12 southern California communities. Cases were defined as physician-diagnosed asthma by age 5, and controls were asthma-free at study entry, frequency-matched on age, sex, and community of residence and countermatched on in utero exposure to maternal smoking. Telephone interviews were conducted with mothers to collect additional exposure and asthma histories. Conditional logistic regression models were fitted to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Asthma diagnosis before 5 years of age was associated with exposures in the first year of life to wood or oil smoke, soot, or exhaust (OR = 1.74; 95% CI, 1.02-2.96), cockroaches (OR = 2.03; 95% CI, 1.03-4.02), herbicides (OR = 4.58; 95% CI, 1.36-15.43), pesticides (OR = 2.39; 95% CI, 1.17-4.89), and farm crops, farm dust, or farm animals (OR = 1.88; 95% CI, 1.07-3.28). The ORs for herbicide, pesticide, farm animal, and crops were largest among children with early-onset persistent asthma. The risk of asthma decreased with an increasing number of siblings (ptrend = 0.01). Day care attendance within the first 4 months of life was positively associated with early-onset transient wheezing (OR = 2.42; 95% CI, 1.28-4.59). In conclusion, environmental exposures during the first year of life are associated with childhood asthma risk.