Epidemiology of physician-diagnosed allergic rhinitis in childhood.

OBJECTIVE: To investigate the natural history of and risk factors for allergic rhinitis in the first 6 years of life. METHODS: Parents of 747 healthy children followed from birth completed a questionnaire when the child was 6 years old. Data were obtained regarding physician-diagnosed allergic rhinitis (PDAR), associated symptoms, and age at onset. Risk-factor data were taken from earlier questionnaires, and data regarding immunoglobulin E (IgE) and skin-test reactivity were obtained at age 6. RESULTS: By the age of 6, 42% of children had PDAR. Children whose rhinitis began in the first year of life had more respiratory symptoms at age 6 and were more likely to have a diagnosis of asthma. Early introduction of foods or formula, heavy maternal cigarette smoking in the first year of life, and higher IgE, as well as parental allergic disorders, were associated with early development of rhinitis. Risk factors for PDAR that remained significant in a multivariate model included maternal history of physician-diagnosed allergy (odds ratio: 2.2, 95% confidence interval: 1.35-3.54), asthma in the child (4.06, 2.06-7.99), and IgE greater than 100 IU/mL at age 6 (1.93, 1.18-3.17). The odds for atopic as opposed to nonatopic PDAR were significantly higher only among those with high IgE and those who had dogs. CONCLUSION: Allergic rhinitis developing in the first years of life is an early manifestation of an atopic predisposition, which may be triggered by early environmental mental exposures.

Exclusive breast-feeding for at least 4 months protects against otitis media.

OBJECTIVE: This study was designed to assess the relation of exclusive breast-feeding, independent of recognized risk factors, to acute and recurrent otitis media in the first 12 months of life. METHODS: Records of 1220 infants who used a health maintenance organization and who were followed during their first year of life as part of the Tucson Children's Respiratory Study were reviewed. Detailed prospective information about the duration and exclusiveness of breast-feeding was obtained, as was information relative to potential risk factors (socioeconomic status, gender, number of siblings, use of day care, maternal smoking, and family history of allergy). Acute otitis media and recurrent otitis media, defined as three or more episodes of acute otitis media in a 6-month period or four episodes in 12 months, were the outcome variables. RESULTS: Of the 1013 infants followed for their entire first year, 476 (47%) had at least one episode of otitis and 169 (17%) had recurrent otitis media. Infants exclusively breast-fed for 4 or more months had half the mean number of acute otitis media episodes as did those not breastfed at all and 40% less than those infants whose diets were supplemented with other foods prior to 4 months. The recurrent otitis media rate in infants exclusively breast-fed for 6 months or more was 10% and was 20.5% in those infants who breast-fed for less than 4 months. This protection was independent of the risk factors considered. CONCLUSION: These findings suggest that exclusive breast-feeding of 4 or more months protected infants from single and recurrent episodes of otitis media.

Child day care, smoking by caregivers, and lower respiratory tract illness in the first 3 years of life. Group Health Medical Associates.

BACKGROUND: Day-care attendance has been associated with an increased risk of hospitalization for lower respiratory tract illnesses (LRIs). This study examines, in a health maintenance organization population of children, the associations between child day care and the occurrence of LRIs in the first 3 years of life. Smoking by caregivers and a possible protective effect of longer day-care enrollment in relation to LRIs are also addressed. METHODS: Information on day-care arrangements was elicited from 1006 parents of infants for five age intervals in the first 3 years of life: birth through 3 months, 4 to 6 months, 6 to 12 months, 1 to 2 years, and 2 to 3 years. Data on LRIs in the first 3 years of life were recorded by pediatricians at the time of the acute illnesses. RESULTS: After controlling for other risk factors, the presence of three or more unrelated children in the care setting was associated with significant risks of LRI of up to twofold or more from 4 months of age to 3 years. Type of care setting was not a significant risk factor during this time period. In the third year of life, the risk of wheezing LRI in the presence of a smoking caregiver was more than threefold for those in another residential home setting. No significant protective effect against LRIs in the third year of life associated with longer prior day-care enrollment was demonstrated. CONCLUSION: The presence of three or more unrelated children in the care setting and the presence of a smoking caregiver were significant independent risk factors for LRIs during the first 3 years of life. Prolonged day-care did not protect against LRIs in the third year of life.

Passive smoke exposure and otitis media in the first year of life. Group Health Medical Associates.

OBJECTIVE: This study examined, in a health maintenance organization population of children, the associations between parents' smoking and otitis media (OM) in their children while controlling for other known risk factors. METHODS: Healthy newborns (1246) in a large health maintenance organization were enrolled at birth, and 1013 (81%) were followed prospectively for the first year of life. Their medical records were reviewed for the diagnosis of otitis media. Information on risk factors for recurrent OM (ROM) was collected, including a number of variables related to parental smoking. RESULTS: After controlling for other known risk factors for ROM including gender, day care, other siblings in the home, parental history of hay fever, and method of feeding, it was found that heavy maternal smoking of 20 or more cigarettes per day was a significant risk factor for ROM but not for nonrecurrent otitis. Heavy maternal smoking was associated with a threefold risk for ROM if the infant weighed less than the mean at birth (3.5 kg) after controlling for other risk factors. No association was found with paternal smoking. CONCLUSIONS: Heavy maternal smoking is a significant risk factor for ROM in the first year of life. This smoking effect seems to be stronger among infants of lower birth weight.

Segregation analyses and a genome-wide linkage search confirm genetic heterogeneity and suggest oligogenic inheritance in some Milroy congenital primary lymphedema families.

We previously described six families with Milroy congenital lymphedema, only one of which showed possible linkage to a candidate locus on chromosome 5 [Witte et al., 1998]. We have now performed a complex segregation analysis of these families, and performed linkage analyses with the other 387 markers used in our genome-wide search. Our results confirm that Milroy lymphedema is generally inherited as a dominant condition. However, this mode of inheritance, as elucidated from the segregation analyses, did not account for all observed familial correlations. The segregation analysis also suggested that shared environmental or additional genetic factors are important in explaining the observed familial aggregation. The finding of linkage to multiple locations in the largest family studied by multipoint parametric mapping (one of which was confirmed by sib-pair non-parametric mapping), suggests that Milroy congenital lymphedema may be oligogenic in this family.

Respiratory effects in relation to estimated tar exposure from current and cumulative cigarette consumption.

Relationships between estimated "tar" exposure from current and past cigarette consumption, were related to respiratory symptoms and function during the seventh survey (1981-1983) of the Tucson epidemiologic study of airways obstructive diseases. Smokers (n = 582; 280 males and 302 females) and exsmokers (n = 621; 345 males and 276 females), answered detailed questions on current and past smoking, and performed flow-volume maneuvers. Cough and phlegm were significantly associated with estimated "tar" exposure from current cigarette consumption. Cough, phlegm, and dyspnea were associated with reported deep inhalation in both sexes, while wheeze was so associated in females. In young smokers (less than 35 years), symptoms were more prevalent in those who had predominantly smoked cigarettes with estimated high "tar." Total exposure was more important in older smokers. Generally, exsmokers showed a lower prevalence of symptoms than smokers. Cross-sectional lung function measurements were significantly related to total estimated "tar" exposure and age. Multiple logistic regressions provided models which helped predict symptoms and lung function impairment in smokers and exsmokers on the basis of estimated "tar" exposure and pack-years of smoking.

Acute lower respiratory illnesses during the first three years of life: potential roles for various etiologic agents. The Group Health Medical Associates.

Lower respiratory tract illnesses (LRIs) occurring during the first 3 years of life among children enrolled in the Tucson Children's Respiratory Study have been studied for evidence of viral, mycoplasmal and Chlamydia trachomatis infections. This report examines those from whom adequate acute and convalescent sera were available at the time of the LRI. Two groups were compared: those in whom culture and/or antigen detection yielded an etiologic agent (N = 110); and those who did not (culture negative, N = 124). Seroconversions (> or = 4-fold titer rise) to respiratory syncytial virus; influenza virus types A and B; parainfluenza virus types 1, 2 and 3; or adenovirus were found in only 0 to 5% of the culture negative group. No significant differences between groups with regard to frequencies of seroconversion to influenza type C, parainfluenza virus type 4, human coronaviruses 229E and OC43 or cytomegalovirus were detected, which suggests that these agents may not be frequent primary causes of LRIs among otherwise healthy children. Significant differences in seroconversions to Epstein-Barr virus were detected, suggesting that Epstein-Barr virus may contribute to LRI morbidity; however, its exact role remains to be defined.

Respiratory syncytial virus-associated lower respiratory illnesses: possible influence of other agents. The Group Health Medical Associates.

Acute lower respiratory illnesses were prospectively investigated in a cohort of 1246 healthy infants who were enrolled at birth in the Tucson Children's Respiratory Study and followed through the first 3 years of life. Respiratory syncytial virus (RSV) infection was documented by culture, antigen detection or both in 276 episodes. In 21 (7.6%) of these 276, other viruses were simultaneously detected. Further serologic studies of 50 episodes in which RSV had been found increased the apparent viral codetection rate to 24%. When culture results for Chlamydia trachomatis and Mycoplasma pneumoniae were also considered, the rate of codetection was found to be 10.9% (30 of 276); this increased to 28% for the subgroup of episodes (14 of 50) that was further studied serologically. Illnesses associated with more than one agent were not significantly different from those involving RSV alone, with respect to month of onset, age at illness, illness type or duration of illness. We conclude that when RSV has been detected in previously healthy infants, routine searches for the concomitant presence of other viruses are usually not warranted.

Multivariate analysis of ambient environmental factors and respiratory effects.

Relationships between respiratory health and environmental conditions (pollen, pollution and meteorology) are investigated in 204 subjects in four symptom groups in four geographical clusters in Tucson. Techniques used are principal components, factor and path analysis. Daily respiratory symptoms and peak expiratory flows were recorded during a three-year period. Ambient pollutants, meteorological conditions and pollen types were monitored in or near the clusters. Factor-based scales, which are climate and season specific, are developed for the environmental variables. Three pollutant/meteorological scales represent 'Summer', 'Winter', and 'Humidity'. Four pollen scales represent early and late spring, summer and fall pollen types. Relationships between environmental variables, respiratory symptoms and peak expiratory flow are analyzed with path diagrams, after accounting for age, sex, smoking habits and stove type. The different effects of the environment on asthmatics, allergics and airways obstructive disease subjects have been demonstrated. Many relationships were found between environmental factors and respiratory responses. The pollutant and meteorological variables are related to respiratory symptoms and peak flow directly as well as through interactions with pollen types. Some of the largest positive coefficients are seen in association with seasonal pollen types, specifically, rhinitis and dyspnoea.

Relationship of infant feeding to recurrent wheezing at age 6 years.

OBJECTIVES: To investigate the relationship of infant feeding to recurrent wheezing at age 6 years and to assess whether this relationship is altered by a history of wheezing lower respiratory tract illnesses. DESIGN: Prospective, longitudinal study of healthy infants followed up from birth to 6 years of age. SETTING: Nonselected health maintenance organization population in Tucson, Arizona. PARTICIPANTS: There were 1246 healthy infants enrolled at birth, 988 of whom had data on both infant feeding and wheezing at age 6 years. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Recurrent wheeze (four or more episodes in the past year) was assessed by a questionnaire that was completed by parents when the children were 6 years old. Children were classified by atopic status on the basis of skin prick tests. RESULTS: Breast-feeding information was collected prospectively, and lower respiratory tract illnesses in the first 3 years of life were diagnosed by the pediatrician. Being breast-fed was associated with lower rates of recurrent wheeze at age 6 years (3.1% vs 9.7%, P < .01) for nonatopic children; this relationship was not significant for atopic children. The relationship of breast-feeding with recurrent wheeze was apparent among nonatopic children both with and without a wheezing lower respiratory tract illness in the first 6 months of life. When potential confounders, including early wheezing lower respiratory tract illness, were included in a multivariate model, nonatopic children who had not been breast-fed had three times the odds of wheezing recurrently (odds ratio, 3.03; confidence interval, 1.06 to 8.69). Eleven percent of recurrent wheeze among nonatopic children could be attributed to not breast-feeding. CONCLUSIONS: Recurrent wheeze at age 6 years is less common among nonatopic children who were breast-fed as infants. This effect is independent of whether the child wheezed with a lower respiratory tract illness in the first 6 months of life.

Differential rates of lung growth as measured longitudinally by pulmonary function in children and adolescents.

A sample population of 67 males and 71 females with longitudinal lung function and other anthropometric measurements from all non-Hispanic white children in the Tucson Epidemiological Study of Airway Obstructive Diseases (AOD) was studied to evaluate biological determinants of the rate of lung growth. Groups within gender were defined by the following factors: 1) maximum height, 2) age at maximum forced expiratory volume at 1 second (FEV1), 3) % predicted initial FEV1 or FEV1/FVC ratio. Only groups defined by low initial function (FEV1 or FEV1/FVC less than or equal to 85% predicted versus greater than 85% predicted) showed statistically significant differences from those with more "normal" function by comparing their maximum % of predicted FEV1s and FEV1/FVC ratios. The longitudinal FEV1 data by age for the latter groups were characterized by a mathematical model (polynomial smoothing spline) yielding optimal fitted curves and an estimate of each group's growth velocity curve. The statistical comparisons between these fitted curves indicate that subjects with low initial pulmonary function continued to have significantly lower FEV1 values for males older than 13.12 years and for females between 8.23 and 15.3 years. At post-hoc analysis persistent wheezing was more likely in the initially more impaired group. Disease at the end of follow-up was not related to initial functional status.

Effects of passive smoking on lung growth in children.

The objective of this study was to determine the effects of passive smoking on functional lung growth in children and adolescents. It was hypothesized that passive smoking might reduce lung function growth, especially in susceptible children. The assumption was that those most susceptible would be children who started with low lung function, as it had been shown that they had slower growth of lung function, and start to decline earlier. There were 138 non-Hispanic Caucasian children and adolescents, ages 5 through 15, who had at least three satisfactory longitudinal lung function tests over a 13 year period in the Tucson epidemiological study of airway obstructive diseases. Those who started in childhood with normal function did not show any effect of passive smoking, nor did females who started with low lung function. Males starting with low lung function whose parents smoked showed definite changes. Their forced expiratory volume in 1 second (FEV1) grew even more slowly between ages 13 through 16, related primarily to continuous parental smoking. They also had higher rates of decline for FEV1 to forced vital capacity (FVC) ratio and maximum flow at 50% vital capacity to FVC ratios than either the low function group without passive smoking or the normal function groups. This was independent of any symptoms or diagnoses present in this male low function group.

Parental childhood respiratory illness and respiratory illness in their infants. Group Health Medical Associates.

Parental histories of childhood respiratory trouble (CRT) were examined as risk factors for lower respiratory tract illnesses in healthy infants enrolled in the Children's Respiratory Study, Tucson, Arizona. A parental history of childhood respiratory trouble before age 16 was a risk factor for infantile lower respiratory tract illnesses (LRIs). Early age of onset of the parental CRT and those illnesses described as asthma or bronchiolitis showed the greatest risk: odds ratio = 2.8, P < 0.05. After controlling for known and suspected confounders, a parental history of CRT described as asthma or bronchiolitis with onset before age 3 was associated with wheezing LRIs in their children, with an odds ratio of 2.6, P < 0.05. A parental history of CRT described as bronchitis/croup was associated with nonwheezing LRIs in their children: odds ratio = 2.2, P < 0.05. These findings suggest a familial component to childhood respiratory trouble which may have a hereditary basis.

Physiological changes in pulmonary development related to passive smoking and its interaction with active smoking.

The growth of pulmonary function between ages 5.5 and 25 years was determined in 1502 observations on 362 subjects from a representative population study of non-Mexican American whites in Tucson. There was an average of 8.8 years of follow-up, with a maximum of 12. The model developed was robust for follow-up of 3-7 observations (3 + years). Respiratory illnesses and smoking had the biggest negative impact on growth of forced expiratory volume in 1 s (FEV1), Vmax 50%/forced vital capacity (FVC) parental smoking and airway obstructive disease (AOD) were important also. Flow measures showed present and more persistent effects of disease and smoking than did FEV1.

Maternal asthma status alters relation of infant feeding to asthma in childhood.

The relation of infant feeding to childhood asthma is controversial. This study tested the hypothesis that maternal asthma alters the relation of breastfeeding to childhood asthma. Questionnaires were completed at age 6, 9 or 11 years by parents of 1043 children enrolled at birth. Active MD asthma was defined as a physician diagnosis of asthma plus asthma symptoms reported on one of the questionnaires. Duration of exclusive breastfeeding, categorized as never, < 4 months, or > or = 4 months, was based on prospective physician reports or questionnaires completed at 18 months. The relationship between breastfeeding and asthma differed by maternal asthma status. For children with maternal asthma, the percent developing active MD asthma increased significantly with longer duration of exclusive breastfeeding. Odds of developing asthma among these children were significantly elevated (OR: 5.7,CI: 2.8-11.5), after adjusting for confounders. This association of longer exclusive breastfeeding with increased risk of reported asthma among children with asthmatic mothers may be biologically based, or may reflect reporting biases.

Breast feeding and lower respiratory tract illness in the first year of life. Group Health Medical Associates.

OBJECTIVE: To assess the relation between breast feeding and subsequent experience of lower respiratory tract illness. DESIGN: Prospective (from well child visits) and retrospective (from maternal recall) study of breast feeding and prospective assessment by paediatricians of lower respiratory tract illness in infants during first year of life. SETTING: Health maintenance organisation. PARTICIPANTS: Over 1000 infants who were healthy at birth and whose parents used the paediatricians of a local health maintenance organisation. MAIN OUTCOME MEASURES: Duration of breast feeding and type of lower respiratory tract illness (wheezing and non-wheezing) at different age intervals during the first year of life. RESULTS: Breast feeding was associated with a decreased incidence of wheezing illnesses only in the first four months of life. Interactions existed between breast feeding and sharing a room, being Mexican American, and being a boy. Multivariate techniques showed that after controlling for a variety of factors children who received minimal breast milk had a greater risk of early wheezing illnesses; the risk was further increased by simultaneous exposure to sharing a room. CONCLUSION: Breast feeding seems to protect against wheezing respiratory tract illnesses in the first four months of life, particularly when other risk factors are present.

Effects of parental smoking and other risk factors on the development of pulmonary function in children and adolescents. Analysis of two longitudinal population studies.

Two sets of longitudinal pulmonary function data have been analyzed to determine the effects of parental smoking on the development of lung function in children and adolescents. One community population was obtained in East Boston, Massachusetts, and one in Tucson, Arizona; both studies started in the 1970s and are still continuing. These data sets, analyzed by different methods, have yielded different answers in regard to the effects of parental smoking. A common analytical approach is now used to determine whether the different outcomes were due to the different analytical methods previously used. These results were compared with results from a similar parallel analysis conducted by the East Boston investigators and indicate that the differences found were not due to the methods used for analysis. Reasons for the differences found are explored. The most likely factor responsible for the disparate results is the exposure difference in the two populations, related to proportion and amount of maternal smoking and different indoor environments.

Comparisons of spirometric reference values and the proportions of abnormal subjects among male smokers and those symptomatic in a community population.

A comparison was performed of various population reference equations for several spirometric measurements. The objective was to determine if the different equations yielded similar distributions of the percent predicted values, similar reference values for asymptomatic nonsmokers (i.e., normal subjects), criteria (or cutoff points) for who might be defined statistically as normal, and similar proportions of smokers and symptomatic subjects who would fall below the criteria values and thus be considered statistically abnormal. The cross-sectional study population of adults in Tucson, subjects of an ongoing study, was used. Most of the equations yielded reasonably similar distributions of percent predicted values. Older and/or more unusual equations did not yield similar results. Using the lower 95th percentile criteria yielded similar cutoff points as reference values for statistical normality, and similar proportions of statistically abnormal among various smoking and symptomatic groups; some of the equations used did not. When the criteria used were the lower 1.645 SEE, or the published criteria, the proportions considered statistically abnormal were very low or very high; again, some equations gave very disparate results. The first conclusion was that the use of the lower 95th percentile criteria was more sensitive and specific. It was concluded also that most equations yield sufficiently similar results such that the choice of reference equation from those available would depend on other criteria.

Time series analyses of respiratory responses to indoor and outdoor environmental phenomena.

A time series analysis was utilized to evaluate respiratory responses to outdoor and indoor air pollutant and aeroallergen exposures in potentially sensitive adults in a dry arid environment. Daily symptoms and peak flows were recorded in populations of asthmatics, allergic individuals, those with chronic lung disease symptoms, and asymptomatic individuals (total sample size of 204) over a period of a few years. Meteorology and ambient pollutant concentrations were measured in the basin. Indoor pollutant measurements were made for particulates and CO, indicating that gas stoves and tobacco smoking were the predominant indoor sources. Time series analysis helped determine appropriate lags between environmental stimuli and health responses. Asthmatics showed that most respiratory responses while asymptomatics showed no significant responses. Outdoor ozone, nitrogen dioxide, aeroallergens and meteorology, and indoor gas stoves were significantly related, independently and interactively, with symptoms and peak flow.

A longitudinal study of risk factors in asthma and chronic bronchitis in childhood.

The prevalence, persistence, incidence and remission rates of reported diagnosed asthma and chronic bronchitis has been studied longitudinally over ten years in a representative community sample of children and adolescents. The objectives are to evaluate the rates of change over time, the role of family history of disease, and the social risk factors in the longitudinal course of disease. The relationship between the two reported diagnoses is very high, about half of each group having the other diagnosis. Each diagnosis has specific symptoms with which it is associated. Remission of clinical disease is associated with continuing symptoms in about half of such cases. The incidence rates and remissions of cases as they have occurred over time were associated with different symptoms and risk factors. A family history of lung disease and family social characteristics are significant risk factors affecting the presence of these diseases, and how they change. Discussion suggests these factors may affect possible precursors, such as lower respiratory tract illnesses, as well as personal habits (such as smoking), which are related to both diagnoses. Further, the interactions of these risk factors appear to significantly influence impairments of lung function at the beginning of adult life, and potential subsequent disease.