Wheeze In Early Childhood Research Articles

Asthma trajectories in early childhood: identifying modifiable factors.

BackgroundThere are conflicting views as to whether childhood wheezing represents several discreet entities or a single but variable disease. Classification has centered on phenotypes often derived using subjective criteria, small samples, and/or with little data for young children. This is particularly problematic as asthmatic features appear to be entrenched by age 6/7. In this paper we aim to: identify longitudinal trajectories of wheeze and other atopic symptoms in early childhood; characterize the resulting trajectories by the socio-economic background of children; and identify potentially modifiable processes in infancy correlated with these trajectories.Data and MethodsThe Millennium Cohort Study is a large, representative birth cohort of British children born in 2000–2002. Our analytical sample includes 11,632 children with data on key variables (wheeze in the last year; ever hay-fever and/or eczema) reported by the main carers at age 3, 5 and 7 using a validated tool, the International Study of Asthma and Allergies in Childhood module. We employ longitudinal Latent Class Analysis, a clustering methodology which identifies classes underlying the observed population heterogeneity.ResultsOur model distinguished four latent trajectories: a trajectory with both low levels of wheeze and other atopic symptoms (54% of the sample); a trajectory with low levels of wheeze but high prevalence of other atopic symptoms (29%); a trajectory with high prevalence of both wheeze and other atopic symptoms (9%); and a trajectory with high levels of wheeze but low levels of other atopic symptoms (8%). These groups differed in terms of socio-economic markers and potential intervenable factors, including household damp and breastfeeding initiation.ConclusionUsing data-driven techniques, we derived four trajectories of asthmatic symptoms in early childhood in a large, population based sample. These groups differ in terms of their socio-economic profiles. We identified correlated intervenable pathways in infancy, including household damp and breastfeeding initiation.

Prenatal and infant exposure to acetaminophen and ibuprofen and the risk for wheeze and asthma in children

Several studies have reported an association between use of over-the-counter antipyretics during pregnancy or infancy and increased asthma risk. An important potential limitation of these observational studies is confounding by indication. We investigated the association of antipyretic intake during pregnancy and during the first year of life (infancy) with asthma-related outcomes before and after controlling for early-life respiratory tract infections. We included 1490 mother-child pairs in Project Viva, a longitudinal prebirth cohort study. We categorized prenatal acetaminophen exposure as the maximum intake (never, 1-9 times, or ≥10 times) in early pregnancy or midpregnancy and ibuprofen intake as presence or absence in early pregnancy. We expressed intake of antipyretics in infancy as never, 1 to 5 times, 6 to 10 times, or more than 10 times. We examined the associations of acetaminophen and ibuprofen (per unit increase in exposure category) during pregnancy and infancy with wheeze, asthma, and allergen sensitization in early childhood (3-5 years of age, n = 1419) and midchildhood (7-10 years of age, n = 1220). Unadjusted models showed an increased asthma risk in early childhood for higher infant acetaminophen (odds ratio [OR], 1.21; 95% CI 1.04-1.41) and ibuprofen (OR, 1.35; 95% CI, 1.19-1.52) intake. Controlling for respiratory tract infections attenuated estimates for acetaminophen (OR, 1.03; 95% CI, 0.88-1.22) and ibuprofen (OR, 1.19; 95% CI, 1.05-1.36). Prenatal acetaminophen was associated with increased asthma (OR, 1.26; 95% CI, 1.02-1.58) in early childhood but not midchildhood. Adjustment for respiratory tract infections in early life substantially diminished associations between infant antipyretic use and early childhood asthma. Respiratory tract infections should be accounted for in studies of antipyretics and asthma to mitigate bias caused by confounding by indication.

Nocturnal dry cough in the first 7 years of life is associated with asthma at school age.

Childhood wheeze is an important, well-known risk factor for asthma, yet little is known about the contribution of nocturnal dry cough. We investigated the association of nocturnal dry cough at ages 1-7 years with doctor-diagnosed asthma at 8 years of age, both in the presence and absence of wheeze. Data of 3,252 children from the PIAMA birth cohort were studied. Parents reported the presence of nocturnal dry cough, wheeze, and doctor-diagnosed asthma in the past 12 months yearly, from birth up to the age of 8 years. Nocturnal dry cough without wheeze was significantly associated with doctor-diagnosed asthma at age 8, except for age 1 (range of Relative Risks (RR) at ages 2-7: 1.8 (age 5) - 7.1 (age 7), all P-values <0.048). As expected, wheeze without nocturnal dry cough was strongly associated with doctor-diagnosed asthma at age 8 (range of RR: 2.0 (age 1) - 22.2 (age 7), all P-values <0.003). Of interest, nocturnal dry cough with wheeze showed the strongest association with doctor-diagnosed asthma at age 8 (range of RR: 3.7 (age 1) - 26.0 (age 7), all P-values <0.001). The relative excess risk of asthma at age 8 due to interaction of nocturnal dry cough with wheeze at age 1 year was 1.8 (0.1-3.6, P < 0.01). Nocturnal dry cough and wheeze in early childhood are both independently associated with asthma at school age. The presence of both nocturnal dry cough and wheeze at age 1 almost doubles the risk of asthma at age 8 compared to wheeze alone.

Chronic lung disease of prematurity and early childhood wheezing: Is foetal inflammatory response syndrome to blame?

BackgroundLong-lasting respiratory symptoms have a huge impact on the quality of life in prematurely born children. AimsWe aimed to investigate the perinatal and maternal risk factors involved in the development of chronic respiratory morbidity in preterm infants, with an emphasis on the importance of Foetal Inflammatory Response Syndrome (FIRS). Study designProspective cohort study. SubjectsDemographic, antenatal, delivery and outcomes data were collected from 262 infants with less than 32 completed weeks of gestational age, over a 10-year period. Outcome measuresPresence of chronic lung disease of prematurity and early childhood wheezing. ResultsIn multivariate logistic regression analysis the presence of FIRS appears to be the most important risk factor for both, chronic lung disease of prematurity (OR 31.05, 95% CI 10.7–87.75, p<0.001) and early childhood wheezing (OR 5.63, 95% CI 2.42–13.05, p=0.01). In the alternative regression model for early childhood wheezing, with chronic lung disease included as a variable, the statistical significance of FIRS completely vanished (OR 1.15, 95% CI 0.39–3.34, p=0.79), whilst chronic lung disease became the most important risk factor (OR 23.45, 95% CI 8.5–63.25, p<0.001). ConclusionsPrenatal and early neonatal events are of utmost importance in the development of chronic respiratory symptoms in children. The influence of FIRS on the development of chronic respiratory symptoms goes far beyond its impact on gestational age and may be related to direct inflammation-mediated lung tissue damage. CLD appears to be an intermittent step on the way from FIRS to ECW.

Infant gut microbiota and the development of wheeze in early childhood

(10.0%) wheezed on more than one occasion, and 12 infants (7.5%) experienced 3 or more wheezing episodes. Selected taxa were chosen for composition analysis, based on their established associations with other allergic disease outcomes. The genus Clostridium was under-represented among infants with two or more wheezing episodes (p=0.04). Preliminary comprehensive analyses revealed that operational taxonomic units (OTUs) belonging to the Families Ruminococcaceae, Rikenellaceae and Lachnospiraceae were overrepresented among wheezing infants (all p<0.01). Gut microbiota diversity and richness were not significantly associated with wheeze; these findings were unchanged following adjustment for gender, mode of delivery, breastfeeding, and antibiotic exposure. Conclusions In this preliminary analysis, we identified several crude differences in microbiota composition among wheezing infants, although a significant association with overall biodiversity was not observed. The long-term clinical relevance of these changes will be the focus of ongoing studies within the CHILD cohort. Detailed and extended assessment of wheeze (including its severity and association with infection and allergic disease), gut microbiota, and relevant environmental exposures will be conducted at different ages throughout childhood.

Induction of human airway epithelial to mesenchymal transition upon rhinovirus infection

Background Structural changes of the airway, collectively referred to as airway remodeling are believed to be the underlying cause of the airway hyperresponsiveness that is characteristic of asthma. Airway remodeling is characterized by thickening of the subepithelial membrane, goblet cell hyperplasia, angiogenesis, increased smooth muscle mass, and epithelial fragility. Thickening of the subepithelial membrane, due to increased deposition of matrix proteins by fibroblasts/myofibroblasts, has been observed in children even prior to the formal diagnosis of asthma. Recent data have shown that young children who experience episodes of human rhinovirus (HRV)-induced wheezing in early childhood are at increased risk of subsequently developing asthma. The primary site of infection of HRV is the airway epithelium. Recent evidence suggests that the molecular reprogramming of epithelial cells through a process called epithelial to mesenchymal transition (EMT) may contribute to increases in fibroblast/myofibroblast in the asthmatic airway. Therefore, we hypothesize that HRV infection plays a role in early airway remodeling by triggering EMT to produce fibroblasts/myofibroblasts that cause thickening of the subepithelial membrane by depositing matrix proteins. Methods The BEAS-2B human bronchial epithelial cell line was grown in 6-well plates in bronchial epithelial growth medium (BEGM). Prior to experiments, cells were grown for 24 h in BEGM from which hydrocortisone was removed. Cells were exposed to medium (control), or purified HRV-16 alone or in the presence of various growth factors for 120 hours with media and growth factor replacement at 48 and 96 hours. Cell lysates were collected and then analyzed by western blot for protein expression of epithelial and mesenchymal markers. Results BEAS-2B cells that were infected with HRV in the presence of epidermal growth factor (EGF) showed decreased expression of the epithelial marker E-cadherin, and increased expression of the mesenchymal marker vimentin.

Protocadherin-1: epithelial barrier dysfunction in asthma and eczema

Asthma and eczema result from the interaction between genetic susceptibility and environmental exposures. Over the last two decades, genetic studies have led to the identification of multiple susceptibility genes, increasing our understanding of the biological pathways leading to these diseases. Many asthma and eczema susceptibility genes are expressed in epithelial cells of airway mucosa and skin [1]. The epithelium constitutes the first line of defence against allergens and invading microbes. Recently, loss of epithelial integrity has been implicated as an important mechanism leading to both asthma [2] and eczema [3]. In this issue of the European Respiratory Journal , Mortensen et al. [4] report the association of genetic variants in the gene encoding protocadherin-1 ( PCDH1 ) with asthma, wheeze and eczema in (early) childhood in the Danish birth cohort study COPSAC (Copenhagen Studies on Asthma in Childhood). Their studies also suggest a gene–environment interaction of PCDH1 with passive smoke exposure in early childhood in asthma development. These studies expand on previous data reporting a role for PCDH1 polymorphisms in the susceptibility to both asthma [4–7] and eczema [4, 6, 8]. Given the replicated association of PCDH1 with both diseases, this gene might contribute to a biological pathway that constitutes a shared cause for both diseases. Here, we will summarise the cumulative data on PCDH1 polymorphisms in asthma and eczema, and make an attempt to interpret these genetic data in light of PCDH1 expression and function as a contributor to epithelial integrity. In 1993, PCDH1 was originally identified by Sano et al. [9] as protocadherin-42 and was reported to induce cell adhesion upon ectopic membrane expression in a mouse fibroblast L-cell assay. PCDH1 is a member of the δ1 subfamily of the …

Predicting the outcome of early childhood wheeze: mission impossible

Predicting the outcome of early childhood wheeze: mission impossible

Allergen challenge in vivo alters rhinovirus-induced chemokine secretion from human airway macrophages

Allergen challenge in vivo alters rhinovirus-induced chemokine secretion from human airway macrophages

The potential to predict the course of childhood asthma

Many children experience pre-school or early childhood wheezing. In a significant proportion symptoms disappear as the child grows, but others have persistent and troublesome asthma which can be life-long. Tools to predict course of disease in young children are a priority for families and clinicians. This review summarizes evidence from several longitudinal population-based birth-cohort studies that have identified risk factors for persistence and remission of childhood asthma. These factors include clinical characteristics, environmental and other exposures, familial factors, biomarkers of allergic inflammation, measurements of lung function and airway responsiveness, and genetic variants. This review also introduces the concept of polygenic risk and genetic risk scores, and describes results from a recent study that suggests promise for the use of genetic information in predicting the course of childhood asthma. We conclude with a discussion of implications and future directions.

Relationship between breast-feeding and wheeze risk in early childhood in Korean children: based on the fifth Korea National Health and Nutrition Examination Survey 2010-2012

Purpose: There is conflicting evidence concerning the relationship between breast-feeding and development of wheezing in early childhood. Epidemiological evidence for a role of breast-feeding on risk of wheezing is inconclusive. The objective of this study was to investigate the associations between breast feeding and risk of current wheezing in early childhood in Korea. Methods: We combined the fifth Korea National Health and Nutrition Examination Survey data collected from 2010 to 2012 and analyzed 1,011 children from 1 to 3 years olds who had been surveyed in regards to breast-feeding. Multivariate regression analysis was used to identify association among the following variables: presence of current wheezing, feeding types and duration of breast-feeding. Results: Prevalence of exclusive breast-feeding and current wheezing decreased both annually from 2010 to 2012. In the univariate analysis, breast-feeding, formula-feeding, duration of breast-feeding were not associated significantly with current wheezing of children younger than 3 years old. No measureable statistically significant relation was observed among breast-feeding, formula feeding, duration of breast-feeding and risk of current wheezing in the multivariate analysis. Conclusion: The present study showed no statistically significant relationship between breast-feeding and the risk of wheeze in early childhood in Korean children. National prospective study is needed to clarify the role of breast-feeding in development of current wheezing. (Allergy Asthma Respir Dis 2014;2:103-107)

Inhaled corticosteroids and bone mineral density at school age: A follow‐up study after early childhood wheezing

The aim of the study was to evaluate the association between previous use of ICS and bone mineral density (BMD) at school age in a cohort followed after early childhood wheezing. As part of a prospective follow-up study after hospitalization for wheezing at <24 months of age, BMD was measured in 89 children at 12.3 (median) years of age. Data on ICS use were collected by interviewing the parents, and this was supplemented with data from patient records. Cumulative doses and the duration of ICS use were calculated. Areal BMD (BMDareal , g/cm(2) ) was measured by dual energy X-ray absorptiometry (DXA), and apparent volumetric BMD (aBMDvol , g/cm(3) ) was calculated, for the lumbar spine and femoral neck. Weight, height and pubertal stage were recorded. Age, sex, and pubertal stage were significantly associated with BMDareal and aBMDvol of the lumbar spine and BMDareal of the femoral neck. The regular use of ICS for >6 months at age <6 years was associated with a lower BMD of the lumbar spine. A lower BMDareal and aBMDvol of the femoral neck were associated with higher cumulative doses of ICS at age 0-12.3 (median) years. The results were robust to adjustment for age, sex, pubertal stage, height, weight, and use of systemic steroids. ICS use during childhood may be related to a decrease in BMD at late school age. It is important to use the lowest possible ICS dose that maintains adequate asthma control.

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...

Comparison of phenotypes of childhood wheeze and cough in 2 independent cohorts

Among children with wheeze and recurrent cough there is great variation in clinical presentation and time course of the disease. We previously distinguished 5 phenotypes of wheeze and cough in early childhood by applying latent class analysis to longitudinal data from a population-based cohort (original cohort). To validate previously identified phenotypes of childhood cough and wheeze in an independent cohort. We included 903 children reporting wheeze or recurrent cough from an independent population-based cohort (validation cohort). As in the original cohort, we used latent class analysis to identify phenotypes on the basis of symptoms of wheeze and cough at 2 time points (preschool and school age) and objective measurements of atopy, lung function, and airway responsiveness (school age). Prognostic outcomes (wheeze, bronchodilator use, cough apart from colds) 5 years later were compared across phenotypes. When using a 5-phenotype model, the analysis distinguished 3 phenotypes of wheeze and 2 of cough as in the original cohort. Two phenotypes were closely similar in both cohorts: Atopic persistent wheeze (persistent multiple trigger wheeze and chronic cough, atopy and reduced lung function, poor prognosis) and transient viral wheeze (early-onset transient wheeze with viral triggers, favorable prognosis). The other phenotypes differed more between cohorts. These differences might be explained by differences in age at measurements. Applying the same method to 2 different cohorts, we consistently identified 2 phenotypes of wheeze (atopic persistent wheeze, transient viral wheeze), suggesting that these represent distinct disease processes. Differences found in other phenotypes suggest that the age when features are assessed is critical and should be considered carefully when defining phenotypes.

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.

Hyper-responsive T-cell cytokine profile in association with development of early childhood wheeze but not eczema at 2 years

Eczema is a known risk factor for the development of wheeze in childhood. Cord blood T-cell cytokine responses have been shown to be associated with the development of both early childhood eczema and wheeze. Our objective is to study and compare the influence of intrinsic T-cell cytokine responses on the development of wheezing and eczema in the first 2 years of life in a birth cohort of at risk (first degree family with atopic disease) infants. Cord blood samples were collected from 195 eligible subjects of a birth cohort of 253 subjects. The subjects studied were those who developed either wheezing (n = 34) or eczema (n = 29) in the first 2 years of life, and 65 healthy infants served as control. Cytokines from phytohaemagglutinin stimulated mononuclear cells were analyzed using multiplex cytokine assays and the cytokine profiles in the 3 groups were compared. Most of the subjects were non-atopic with only 3/34 (9%) wheeze and 9/29 (31%) eczema subjects sensitized to the common dietary or inhalant allergens. After adjustment for potential risk factors, wheeze, but not eczema subjects, presented with hyper-responsive cytokine profiles with increased production of T-cell cytokines IL-2 and IL-5. IL-5 was the strongest risk factor associated to the development of wheeze at 2 years of age (OR, 35; 95% CI, 5.0 -246.7). Cord blood cytokine responses in early onset wheeze and eczema are distinctly different. This suggests that the tendency to develop early onset wheeze may be influenced by preexisting immune factors independent to those for eczema.

Parental psychological distress during pregnancy and wheezing in preschool children: The Generation R Study

Maternal psychological distress during pregnancy might affect fetal lung development and subsequently predispose children to childhood asthma. We sought to assess the associations of maternal psychological distress during pregnancy with early childhood wheezing. We performed a population-based prospective cohort study among 4848 children. We assessed maternal and paternal psychological distress at the second trimester of gestation and 3 years after delivery and maternal psychological distress at 2 and 6 months after delivery by using the Brief Symptom Inventory questionnaire. Wheezing in the children was annually examined by using questionnaires from 1 to 4 years. Physician-diagnosed ever asthma was reported at 6 years. Mothers with psychological distress during pregnancy had increased odds of wheezing in their children from 1 to 4 years of life (overall distress: odds ratio [OR], 1.60 [95% CI, 1.32-1.93]; depression: OR, 1.46 [95% CI, 1.20-1.77]; and anxiety: OR, 1.39 [95% CI, 1.15-1.67]). We observed similar positive associations with the number of wheezing episodes, wheezing patterns, and physician-diagnosed asthma at 6 years. Paternal distress during pregnancy and maternal and paternal distress after delivery did not affect these results and were not associated with childhood wheezing. Maternal psychological distress during pregnancy is associated with increased odds of wheezing in their children during the first 6 years of life independent of paternal psychological distress during pregnancy and maternal and paternal psychological distress after delivery. These results suggest a possible intrauterine programming effect of maternal psychological distress leading to respiratory morbidity.

To Evaluate Serum Eosinophil Cationic Protein and Total IgE Concomitantly May Predict the Persistence of Wheezing in Young Children

Background. We investigated the predictive value and the relative risk of the evaluation of serum eosinophilic cationic protein (sECP) and total IgE levels concomitantly in relation to the persistence of wheezing in young children. Methods. The study was conducted prospectively between January 2007 and December 2010. A hundred and eight children, aged between three months and four years, with three or more episodes of wheezing, were studied to evaluate the role of eosinophil inflammation and its relation to persistence of wheezing two years later. Results. A statistically significant difference in terms of total IgE and sECP values was observed between the groups (P < 0.05). When measurement of IgE and sECP was assessed concomitantly, the sensitivity was found to be 92.68%, the negative predictive value was found to be 71.43%, accuracy rate was found to be 84.26%, and the relative risk was found to be 3.06 in group 1. Conclusions. In this study, we aimed to emphasize the importance of the assessment of sECP and total IgE concomitantly, as being two noninvasive and easily applicable tests, useful in predicting persistent wheezing in early childhood.

Fetal Smoke Exposure and Risks of Wheezing During Early Childhood

Source: Duijts L, Jaddoe VWV, van der Valk RJP, et al. Fetal exposure to maternal and paternal smoking and the risks of wheezing in preschool children: the Generation R Study. Chest. 2012; 141(4): 876– 885; doi: 10.1378/chest.11-0112Investigators from the Netherlands examined the association between maternal and paternal smoking during pregnancy and the risk of early childhood wheezing. Data were collected as part of the Generation R Study,1 a large prospective cohort study in the Netherlands. Study children were born between 2002 and 2006. Mothers reported on smoking habits of both mother and father at the time of the first routine prenatal ultrasound. Smoking habits during second and third trimesters were assessed by follow-up questionnaires. Maternal smoking habits were categorized as “never during pregnancy,” “first trimester only,” and “continued during pregnancy,” while fathers’ smoking habits were categorized as yes/no during pregnancy. Data on childhood wheezing were collected annually on study children between the ages of 1 to 4 years based on parental report. Rates of wheezing in children of parents with different prenatal smoking patterns were compared after accounting for confounding variables such as family history of asthma or atopy, gestational age, day care attendance, and postnatal smoke exposure.Mothers of 6,969 children were enrolled in the study and data on 4,574 children analyzed. Nine percent of mothers reportedly smoked in the first trimester and 14% continued smoking during pregnancy. Compared to children of mothers who never smoked, children of mothers who continued smoking during pregnancy had a higher risk of wheezing at all ages (P < .05). These children were also at increased risk for frequent wheezing (≥4 episodes per year) during the first 3 years of life (OR=1.64, 1.64, 2.19). These findings were independent of the child’s postnatal smoke exposure or size for gestational age. Neither maternal smoking limited to the first trimester nor paternal smoking were associated with a significant increase in childhood wheezing.The authors conclude that continued maternal smoking during pregnancy is associated with increased risks of wheezing in early childhood.Dr Kier has disclosed no financial relationship relevant to this commentary. This commentary does not contain a discussion of an unapproved/investigative use of a commercial product/device.The risks of environmental tobacco smoke have been well-documented in the pediatric literature.3,4 Smoking habits of parents are routinely assessed by pediatricians and counseling on smoking cessation is an important component of anticipatory guidance. But how early do we “intervene”? Prior retrospective studies have documented that adverse effects may be as early as exposure in utero.5,6 This prospective study includes data from early pregnancy. Thus, the duration and timing of smoking during pregnancy was identified. Paternal smoking was differentiated from maternal smoking with a number of confounding factors also analyzed. More importantly, postnatal smoke exposure and being small for gestational age were specifically accounted for and found to be independent of the association of fetal exposure and wheezing. Based on this study, one could speculate that there are direct adverse effects of maternal smoke exposure on the developing fetal lung. The limitation of this epidemiologic study, though, is that this remains a speculation until these adverse effects in the fetal human lung are directly identified by future laboratory studies. This study was further limited by the fact that data were based on questionnaires. In addition, smoking may have been underreported because there were no biomarkers used, and there were no direct measures of wheezing.The take-home message of this study is that there is an opportunity for early counseling. It is never too late to quit smoking when identified during the first trimester of pregnancy. Obstetricians have been our reliable partners in preventive health; it would be worth developing joint guidelines to address this major health care concern and to jointly support tobacco-dependence programs for pregnant women.7 How early can “intervention” occur? Based on this study, well before a prenatal visit to the obstetrician.One of the criteria for ascribing causation with a finding of an association between an exposure and an outcome is biologic plausibility. As is pointed out in the commentary above, there is no known biologic explanation for why exposure to tobacco in the second and third trimesters leads to wheezing. An alternative explanation of the major finding of this study is that smoking throughout pregnancy is merely a marker for postnatal exposure to tobacco smoke and that it is this postnatal exposure that was the exposure that led to increased childhood wheezing. Perhaps the authors failed to adequately control for postnatal exposure in their analyses and/or there was misclassification of postnatal smoke exposure (ie, data on postnatal exposure were inaccurate).

The association between tobacco and the risk of asthma, rhinoconjunctivitis and eczema in children and adolescents: analyses from Phase Three of the ISAAC programme

BackgroundExposure to parental smoking is associated with wheeze in early childhood, but in 2006 the US Surgeon General stated that the evidence is insufficient to infer a causal relationship between...