Dynamic changes in sensitization to specific aeroallergens in children raised in a desert environment.

BACKGROUND: Allergen skin test reactivity and total serum IgE are objective measures used to characterize and help diagnose allergic diseases. Cross-sectional studies have shown that overall aeroallergen skin test reactivity increases throughout childhood. However, little attention has been paid to whether individual aeroallergen remittance occurs, which could distort or mask relationships to disease. OBJECTIVE: To access the incidence and remittance of skin test reactions to individual allergens in children aged 6-11 years. METHODS: Longitudinal sensitization to six aeroallergens and total IgE were assessed in 828 children raised in the semi-arid US southwest at ages 6 and 11 years. RESULTS: New sensitization (to any allergen) between 6 and 11 years occurred in 30.2% of children compared with 39.7% before age 6 years. The rate of complete remittance from positive to negative between ages 6 and 11 years was 8.2%, and total IgE at age 6 years was not predictive. Remittance rates for individual allergens were high and variable (19-49%). The perennial allergens Bermuda and Alternaria were early sensitizers and had low remittance rates. Early sensitization to the four seasonal allergens was less common and more subject to remittance with the bulk of sensitization occurring between 6 and 11 years. CONCLUSION: This study shows that sensitization to individual aeroallergens in childhood is dynamic and indicates the limitation of single point assessment of skin test reactivity.

Relation between infantile colic and asthma/atopy: a prospective study in an unselected population.

OBJECTIVE: To assess whether children with history of infantile colic may be at increased risk of subsequently developing asthma and/or atopy. METHODS: We used data collected in a large, prospective study from an unselected population. Infantile colic and concurrent feeding method were determined from the 2-month well-infant visit form completed by the physician for 983 children who were enrolled at birth. Markers of atopy (total serum immunoglobulin E and allergy skin prick test), allergic rhinitis, asthma, wheezing, and peak flow variability were the main outcome measures studied at different ages between infancy and 11 years. RESULTS: Ninety (9.2%) children had infantile colic. Prevalence of colic was similar among children fed either breast milk or formula. There was no association between infantile colic and markers of atopy, asthma, allergic rhinitis, wheezing, or peak flow variability at any age. CONCLUSION: Our data cannot support the hypothesis that infantile colic provides increased risk for subsequent allergic disease or atopy.

Relation of two different subtypes of croup before age three to wheezing, atopy, and pulmonary function during childhood: a prospective study.

OBJECTIVE: Some retrospective evidence suggests that children with a history of croup may be at increased risk of subsequently developing asthma, atopy, and diminished pulmonary function. The objective of this study was to determine the long-term outcome of croup (as diagnosed by a physician) in early life. METHODS: Lower respiratory illnesses (LRIs) in the first 3 years of life were assessed in 884 children who were enrolled in a large longitudinal study of airway diseases at birth. Pulmonary function tests, markers of atopy, and wheezing episodes were studied at different ages between birth and 13 years. RESULTS: Ten percent of children had croup with wheeze (Croup/Wheeze), 5% had croup without wheeze (Croup/No Wheeze), 36% had another LRI (Other LRI), and 48% had no LRI. Respiratory syncytial virus was more frequently isolated in children with Croup/Wheeze and Other LRI than in those with Croup/No Wheeze. There was no association between croup in early life and markers of atopy measured during the school years. Only children with Croup/Wheeze and with Other LRI had a significant risk of subsequent persistent wheeze later in life. Significantly lower levels of indices of intrapulmonary airway function were observed at ages <1 (before any LRI), 6, and 11 years in children with Croup/Wheeze and Other LRI compared with children with No LRI. Conversely, inspiratory resistance before any LRI episode was significantly higher in infants who later developed Croup/No Wheeze than in the other 3 groups. CONCLUSIONS: We distinguish 2 manifestations of croup with and without wheezing. Children who present with croup may or may not be at increased risk of subsequent recurrent lower airway obstruction, depending on the initial lower airway involvement, and preillness and postillness abnormalities in lung function associated with this condition.

Factors influencing the relation of infant feeding to asthma and recurrent wheeze in childhood.

BACKGROUND: The relationship between infant feeding and childhood asthma is controversial. This study tested the hypothesis that the relation between breast feeding and childhood asthma is altered by the presence of maternal asthma. METHODS: Healthy non-selected newborn infants (n = 1246) were enrolled at birth. Asthma was defined as a physician diagnosis of asthma plus asthma symptoms reported on > or = 2 questionnaires at 6, 9, 11 or 13 years. Recurrent wheeze (> or = 4 episodes in the past year) was reported by questionnaire at seven ages in the first 13 years of life. Duration of exclusive breast feeding was based on prospective physician reports or parental questionnaires completed at 18 months. Atopy was assessed by skin test responses at the age of 6 years. RESULTS: The relationship between breast feeding, asthma, and wheeze differed with the presence or absence of maternal asthma and atopy in the child. After adjusting for confounders, children with asthmatic mothers were significantly more likely to have asthma if they had been exclusively breast fed (OR 8.7, 95% CI 3.4 to 22.2). This relationship was only evident for atopic children and persisted after adjusting for confounders. In contrast, the relation between recurrent wheeze and breast feeding was age dependent. In the first 2 years of life exclusive breast feeding was associated with significantly lower rates of recurrent wheeze (OR 0.45, 95% CI 0.2 to 0.9), regardless of the presence or absence of maternal asthma or atopy in the child. Beginning at the age of 6 years, exclusive breast feeding was unrelated to prevalence of recurrent wheeze, except for children with asthmatic mothers in whom it was associated with a higher odds ratio for wheeze (OR 5.7, 95% CI 2.3 to 14.1), especially if the child was atopic. CONCLUSION: The relationship between breast feeding and asthma or recurrent wheeze varies with the age of the child and the presence or absence of maternal asthma and atopy in the child. While associated with protection against recurrent wheeze early in life, breast feeding is associated with an increased risk of asthma and recurrent wheeze beginning at the age of 6 years, but only for atopic children with asthmatic mothers.

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.

Keeping children with exercise-induced asthma active.

Exercise-induced bronchospasm, exercise-induced bronchoconstriction, and exercise-induced asthma (EIA) are all terms used to describe the phenomenon of transient airflow obstruction associated with physical exertion. It is a prominent finding in children and young adults because of their greater participation in vigorous activities. The symptoms shortness of breath, cough, chest tightness, and wheezing normally follow the brief period of bronchodilation present early in the course of exercise. Bronchospasm typically arises within 10 to 15 minutes of beginning exercise, peaks 8 to 15 minutes after the exertion is concluded, and resolves about 60 minutes later, but it also may appear during sustained exertion. EIA occurs in up to 90% of asthmatics and 40% of patients with allergic rhinitis; among athletes and in the general population its prevalence is between 6% and 13%. EIA frequently goes undiagnosed. Approximately 9% of individuals with EIA have no history of asthma or allergy. Fifty percent of children with asthma who gave a negative history for EIA had a positive response to exercise challenge.6 Among high school athletes, 12% of subjects not considered to be at risk by history or baseline spirometry tested positive. Before the 1984 Olympic games, of 597 members of the US team, 67 (11%) were found to have EIA. Remarkably, only 26 had been previously identified, emphasizing the importance of screening for EIA even in well-conditioned individuals who appear to be in excellent health. The severity of bronchospasm in EIA is related to the level of ventilation, to heat and water loss from the respiratory tree, and also to the rate of airway rewarming and rehydration after the challenge. Postexercise decrease in the peak expiratory flow rate of normal children may be as much as 15%; therefore, only a decrease in excess of 15% should be viewed as diagnostic. EIA is usually provoked by a workload sufficient to produce 80% of maximum oxygen consumption; however, in severe asthmatics even minimal exertion may be enough to produce symptoms. Patients with normal lung function at rest may have severe air flow limitation induced by exercise,10 and as many as 50% of patients who are well-controlled with inhaled corticosteroids still exhibit EIA. A challenge of sufficient magnitude will provoke EIA in all patients with asthma. PHARMACOLOGIC THERAPY: Exercise, unlike exposure to allergens, does not produce a long-term increase in airway reactivity. Accordingly, patients whose symptoms manifest only after strenuous activity may be treated prophylactically and do not require continuous therapy. Most asthma medications, even some unconventional ones such as heparin, furosemide, calcium channel blockers, and terfenadine, given before exercise, suppress EIA. McFadden accounts for the efficacy of these disparate classes of drugs by their potential effect on the bronchial vasculature that modulates the cooling and/or rewarming phases of the reaction. Short-acting -agonists provide protection in 80% to 95% of affected individuals with insignificant side effects and have been regarded for many years as first-line therapy. Two long-acting bronchodilators, salmeterol and formoterol, have been found effective in the prevention of EIA.18-21 A single 50-microg dose of salmeterol protects against EIA for 9 hours; its duration appears to wane in the course of daily therapy. Cromolyn sodium is highly effective in 70% to 87% of those diagnosed with EIA and has minimal side effects. Nedocromil sodium provides protection equal to that of cromolyn in children. Children commonly engage in unplanned physical activity and sometimes are not allowed to carry their own medication. Thus, a simple long-acting regimen given at home is likely to be more effective than short-acting drugs that must be administered in a timely manner. Although the 12-hour protection by salmeterol reported by Bronsky et al may not persist with continued use, the 9-hour duration of action is

Respiratory syncytial virus in early life and risk of wheeze and allergy by age 13 years.

BACKGROUND: The relation between lower respiratory tract illnesses in early life caused by the respiratory syncytial virus (RSV) and the subsequent development of wheezing and atopy in childhood is not well understood. We studied this relation in children who had lower respiratory tract illnesses that occurred before 3 years of age. METHODS: Children were enrolled at birth and cases of lower respiratory tract illness were ascertained by a physician. Viral tests were done for specimens collected at the time of the illness. Children were classified into five groups according to type and cause of lower respiratory tract illness. Children were then followed prospectively up to age 13, and we measured frequency of wheezing, pulmonary function, and atopic status (allergy skin-prick tests, serum IgE concentrations). FINDINGS: RSV lower respiratory tract illnesses were associated with an increased risk of infrequent wheeze (odds ratio 3.2 [95% CI 2.0-5.0], p < 0.001), and an increased risk of frequent wheeze (4.3 [2.2-8.7], p < or = 0.001) by age 6. Risk decreased markedly with age and was not significant by age 13. There was no association between RSV lower respiratory tract illnesses and subsequent atopic status. RSV lower respiratory tract illnesses were associated with significantly lower measurements of forced expiratory volume (2.11 [2.05-2.15], p < or = 0.001) when compared with those of children with no lower respiratory tract illnesses, but there was no difference in forced expiratory volume after inhalation of salbutamol. INTERPRETATION: RSV lower respiratory tract illnesses in early childhood are an independent risk factor for the subsequent development of wheezing up to age 11 years but not at age 13. This association is not caused by an increased risk of allergic sensitisation.

Influence of parental smoking on respiratory symptoms during the first decade of life: the Tucson Children's Respiratory Study.

Compelling evidence suggests a causal relation between exposure to parental cigarette smoking and respiratory symptoms during childhood. Still, the roles of prenatal versus postnatal parental smoking need clarification. In this study, the authors assessed the effects of passive smoking on respiratory symptoms in a cohort of over 1,000 children born during 1980-1984. The children were enrolled in the Tucson Children's Respiratory Study in Tucson, Arizona, and were followed from birth to age 11 years. The population was generally middle class and consisted of two main ethnic groups, non-Hispanic Whites (75%) and Hispanics (20%), reflecting Tucson's population. Information on parental smoking and on wheeze and cough in their children was elicited from parents by using questionnaires at five different surveys. Data were analyzed both cross-sectionally and by using the generalized estimation equation approach, a longitudinal mixed-effects model. The best-fitting model indicated that maternal prenatal but not postnatal smoking was associated with current wheeze (odds ratio = 2.3, 95% confidence interval 1.4-3.8) independently of a family history of asthma, socioeconomic factors, and birth weight. This effect was time dependent and significant only below age 3 years; although independent of gender, the association was stronger for girls (odds ratio = 3.6, 95% confidence interval 1.6-8.0). Cough was not associated with parental smoking during the first decade of life. This transitory effect of maternal prenatal smoking on wheezing could be due to changes that affect the early stages of lung development.

Association of radiologically ascertained pneumonia before age 3 yr with asthmalike symptoms and pulmonary function during childhood: a prospective study.

Epidemiologic evidence suggests an association between reports of pneumonia in early life and the subsequent development of diminished lung function. However, no studies are available in which the diagnosis of pneumonia was based on radiologic evidence. Lower respiratory illnesses with or without a radiologically confirmed diagnosis of pneumonia were assessed in a study of 888 children enrolled at birth. Pulmonary function tests, markers of atopy, asthma diagnosis, and prevalence of respiratory symptoms were assessed at different ages between birth and 11 yr. Incidence of pneumonia during the first 3 yr of life was 7.4%. Respiratory syncytial virus was the most frequent agent identified both in children with pneumonia and in those with lower respiratory tract illness (LRI) without pneumonia (36.4% versus 35.6%, respectively). Children with a diagnosis of pneumonia were more likely to have physician-diagnosed asthma and current wheezing at ages 6 and 11 yr than were those who had no LRIs. When compared with children without LRIs, those with a diagnosis of pneumonia had lower levels of maximal flows at FRC at mean age of 2 mo (albeit not significantly) and at age 6 yr, and lower levels of FEV1 and FEF25-75 at age 11 yr. These deficits were independent of known confounders, including wheezing at the time of study, and were partly and significantly reversed after administration of a bronchodilator. We conclude that children with radiologically confirmed pneumonia have diminished airway function that is probably present shortly after birth. These deficits are at least in part due to alterations in the regulation of airway muscle tone.

Differential immune responses to acute lower respiratory illness in early life and subsequent development of persistent wheezing and asthma.

BACKGROUND: Recent epidemiologic evidence suggests that 2 wheezing syndromes coexist in early life: transient wheezing, limited to early childhood, and persistent wheezing, which starts in early childhood and persists beyond that age. OBJECTIVE: Whether the nature of the immune response occurring during acute lower respiratory illnesses (LRIs) in infancy differs between these 2 groups of wheezers has yet to be determined. METHODS: We compared total serum IgE levels and peripheral blood eosinophil counts obtained during the acute phase of the first LRI with those obtained during the convalescent phase or with well-baby samples in persistent (n = 49) and transient early wheezers (n = 88), as well as in children who had only nonwheezing LRIs (n = 43) during the first 3 years of life. RESULTS: Total serum IgE levels were significantly higher (P =.008) during the acute phase compared with the convalescent phase of the LRI in persistent wheezers, a response not observed in transient early wheezers (P =.7). Peripheral blood eosinophil counts were significantly reduced during the acute phase of the LRI (P =.009) in transient early wheezers, a response not observed among persistent wheezers (P =.7). Acute responses in children who had nonwheezing LRIs only were similar to those seen in transient early wheezers. CONCLUSION: Alterations in acute immune response to viral infection may be detected at the time of the first wheezing episode in subjects who will go on to have persistent wheezing symptoms.

Lessons from long-term cohort studies. Childhood asthma.

Cohort studies, which are longitudinal studies that follow a group of people with reference to the development of disease, have been a cornerstone of research on childhood asthma. These studies are uniquely suited to address questions concerning the incidence of illness, the natural history of disease, and the sequence of events linking exposures with outcomes. Three findings from on-going cohort studies are particularly relevant for the design of future intervention studies. First, most childhood asthma begins in infancy, with 80% of children who develop asthma having their first episode of wheeze before the age of 3 yrs. Second, events in early life, possibly including allergen exposure, infant feeding practices and viral infections, may be critical to the development of asthma in childhood. Finally, wheezing presents as separate phenotypes at different ages, with each phenotype having distinct characteristics, risk factors and prognoses. Additional cohort studies are required to determine to what extent events occurring in infancy, both viral and allergic, trigger expression of asthma, what are the mechanisms whereby they foster development of the disease, and whether their effect can be prevented.

Alternaria as a major allergen for asthma in children raised in a desert environment.

The relationships of asthma and allergic rhinitis with individual immediate skin test responses were examined for preferential associations and for changes with age in children raised in a semiarid environment. Prevalence of physician-diagnosed asthma was 9.8% at age 6 (n = 948) and 15.5% at age 11 (n = 895). Immediate skin test responses to Bermuda grass were the most prevalent among children with allergic rhinitis and control subjects, whereas responses to the mold, Altenaria alternata, were the most prevalent among asthmatics. Skin test responses for crude house dust, Dermatophagoides farinae, and cat had low prevalences in all groups. By logistic regression, Alternaria was the only allergen independently associated with increased risk for asthma at both ages 6 and 11. Allergic rhinitis showed independent association with sensitization to Bermuda grass and mulberry tree pollen at age 11 but did not show an independent relation to any single allergen at age 6. Logistic regression further revealed that persistent asthma (diagnosed before age 6) was independently associated with Alternaria skin tests at both ages 6 and 11, whereas new asthma (diagnosed after age 6) was associated with Alternaria skin tests at age 6 but not at age 11. We conclude that Alternaria is the major allergen associated with the development of asthma in children raised in a semiarid environment and that skin test responses at age 6 are more closely linked to asthma than those at age 11.

Peak flow variability, methacholine responsiveness and atopy as markers for detecting different wheezing phenotypes in childhood.

BACKGROUND: There is increasing evidence that wheezing during childhood may be a heterogeneous condition, and that different forms of wheezing may be associated with different risk factors and prognosis. The aim of this study was to determine if measures of airway lability and of atopy could identify distinct wheezing phenotypes during childhood. METHOD: In a cohort of children followed from birth peak flow variability (n = 600) was evaluated and methacholine challenge responsiveness (n = 397) was measured at age 11 in relation to wheezing before the age of three, and at age six and 11 years total serum IgE and skin test reactivity to allergens were determined. RESULTS: Neither positive peak flow variability nor methacholine hyperresponsiveness measured at age 11 were associated with wheezing occurring only during the first three years of life. Both methacholine hyperresponsiveness and positive peak flow variability were associated with wheezing at both ages six and 11 (OR 5.1 (95% CI 2.4 to 10.6) and 2.3 (1.2 to 4.5), respectively). In addition, positive peak flow variability was associated with wheezing up to the age of six but not at age 11 in non-atopic children (OR 2.9 (95% CI 1.0 to 8.8)). Methacholine hyperresponsiveness measured at age 11 was more frequently observed in boys (OR 2.1 (95% CI 1.2 to 3.5)) and was strongly associated with serum IgE levels measured at ages six and 11 (p < 0.001) and with positive skin test reactivity (OR 4.5 (95% CI 2.0 to 10.1)). Peak flow variability was unrelated to sex or markers of atopy (IgE and skin test reactivity). CONCLUSIONS: Methacholine responsiveness and peak flow variability assessed at age 11, together with markers of atopy (IgE and skin test reactivity to allergens) identify three different wheezing phenotypes in childhood: "transient early wheezing" limited to the first three years of life and unrelated to increased airway lability; "non-atopic wheezing" of the toddler and early school years associated with positive peak flow variability but not with methacholine hyperresponsiveness; and "IgE-associated wheeze/asthma" associated with persistent wheezing at any age and with methacholine hyperresponsiveness, peak flow variability, and markers of atopy.

Segregation analysis of physician-diagnosed asthma in Hispanic and non-Hispanic white families. A recessive component?

The inheritance of asthma, evident from its high family concordance, is not well understood. To investigate whether asthma may be inherited through a major gene with two alleles, segregation analyses were conducted in 3,369 individuals from 906 nuclear families enrolled, without selection, in a longitudinal study of respiratory health in Tucson, Arizona. Physician-diagnosed asthma and its age of onset were ascertained for each family member when children were at a mean age of 7 yr. Age of asthma diagnosis was allowed for in analyses, and the impact of the covariate total serum IgE level on age of onset was examined. Segregation analyses were conducted with and without residual family effects, with and without the covariate IgE. The hypothesis of a single two-allele locus for asthma was rejected. However, depending on the method of assessment of the residual familial effects, either a polygenic/multifactorial mode of inheritance alone, or an oligogenic model with some evidence of a recessive component present in the population with the high frequency of 0.67, were compatible with the data. Results were unchanged with the addition of the covariate IgE.

Serum levels of the soluble low affinity receptor for IgE and soluble interleukin-2 receptor in childhood, and their relation to age, gender, atopy and allergic disease.

Identifying immune factors associated with the development of atopy can enhance our understanding of the in vivo mechanisms involved and may have utility in paradigms designed to prevent disease. Two candidates suggested for such roles are the soluble low affinity receptor for IgE (sCD23) and the soluble interleukin-2 receptor (sCD25). To assess serum levels of these factors blood samples were collected at birth and at age 6 in a large nonselected population from Tucson, AZ. Log mean sCD23 and sCD25 levels decreased from birth to age 6, (for sCD23 0.60 ffi 0.26pg/l, n = 340 and 0.53 + 0.28pg/l, n = 333 and for sCD25 1.95 i 0.14pM, n = 304 and 1.86 ffi 0.20pM, n = 327, for the two ages respectively. Anglo children had lower sCD23 levels at birth compared to Hispanic children (p < 0.01); no effect of gender was observed. Skin test reactivity at age 6 was directly related to sCD25 levels at age 6 (p = 0.007) and even levels at birth showed a similar trend (p = 0.06). These relations were distinct from any relation to total serum IgE. No relation was observed with sCD23 levels for either skin test reactivity or serum IgE. The prevalences of asthma, rhinitis and eczema by age 6 were unrelated to sCD25 or sCD23 levels. The results indicate that soluble CD23 and CD25 have higher levels at birth than later in childhood and that the development of skin test reactivity may be associated with regulatory mechanisms involving sCD25, whereas sCD23 was not similarly implicated.

Recurrent cough in childhood and its relation to asthma.

Risk factors for recurrent cough (RC) in childhood, and its relation to asthma were investigated as part of the prospective, longitudinal Tucson Children's Respiratory Study. RC, defined as > or = 2 episodes of cough without a cold in the past year, was assessed by questionnaire in 987 children at age 6. Children having RC without wheeze (n = 154) did not differ from children with neither symptom (n = 610) in serum IgE levels, skin test response, size-corrected forced expiratory flow, or percentage of decline following cold air challenge. In contrast, children with both RC and wheeze (n = 116) had significantly more respiratory illness, more atopy, lower flow at end-tidal expiration (V'maxFRC), and greater declines in lung function following cold air challenge than children with neither symptom. Current parental smoking was a risk for RC without wheeze, whereas male gender, maternal allergy, wheezing lower respiratory tract illness (LRI) in early life, and high IgE were significant risks for RC with wheeze, compared with children having neither symptom. RC early in life resolved in the majority of children, between ages 2-3 yr and age 6, and between age 6 and age 11. High IgE and positive skin prick test were associated with persistence of RC to age 6 among children who wheezed, and markers of allergy were associated with persistence of RC between 6 and 11 yr. These findings suggest that recurrent cough in the absence of wheeze differs in important respects from classic asthma, and using the same label to refer to these distinct syndromes may obscure their diverse pathophysiologies.

Evaporative cooling and other home factors and lower respiratory tract illness during the first year of life. Group Health Medical Associates.

Lower respiratory tract illness (LRI) is associated with exposure to various environmental factors. The relation between home environment and LRI in infants was studied with the use of data from the Children's Respiratory Study in Tucson, Arizona. Healthy infants from a health maintenance organization were recruited at birth (1980-1984). Analysis was restricted to one infant per family, and to those followed through the first year (n=936). Environmental data were collected at enrollment, and clinicians diagnosed LRI according to predetermined criteria. During the first year of life, 196 infants (21%) had wheezing LRI, and 60 (6%) had nonwheezing LRI. The risk of wheezing LRI was higher in infants with evaporative home cooling (24%) than in those without evaporative home cooling (15%) (odds ratio = 1.8, 95% confidence interval 1.1-3.0); this association was stronger among infants who lived with other children in the home. The risk of nonwheezing LRI was associated with parents' rating of neighborhood dustiness, ranging from 5% in the least dusty environments to 12% in the dustiest (p for trend = 0.002). Neither association could be explained by confounding factors. LRI was not related to the type of home heating, cooking fuel, or the numbers of indoor dogs or cats.

Association of interleukin-2 and interferon-gamma production by blood mononuclear cells in infancy with parental allergy skin tests and with subsequent development of atopy.

The mechanisms regulating the onset of atopic sensitization in human beings are not yet fully clarified. We assessed the capacity of mitogen-stimulated umbilical and peripheral blood mononuclear cells to produce interferon-gamma (IFN-gamma) and interleukin-2 (IL-2) at birth and at 9 months of age in 159 infants. Mononuclear cell production of both IFN-gamma and IL-2 at 9 months, but not at birth, was found to be inversely related to parental immediate skin test reactivity to seven local aeroallergens. Skin test reactivity at the age of 6 years was also inversely related to IFN-gamma and IL-2 production at 9 months of age. However, no relationship was evident between total serum IgE levels at 6 years and production of these cytokines at 9 months. The proportions of circulating lymphocytes and CD4+ or CD8+ cells were also unrelated to skin test reactivity at the age of 6 years. These data suggest that mechanisms regulating skin test reactivity to inhaled allergens may involve deficient IFN-gamma production, deficient IL-2 production, or both during or preceding the time of initial sensitization and that additional mechanisms are involved in regulating total serum IgE level.

Association of non-wheezing lower respiratory tract illnesses in early life with persistently diminished serum IgE levels. Group Health Medical Associates.

BACKGROUND: The role of lower respiratory tract illnesses (LRIs) in the development of allergies is not well understood. The relation of wheezing and non-wheezing LRIs to serum IgE levels and atopy was studied in 888 children. METHODS: Total serum IgE levels were measured at birth, nine months and six years of age; and interferon gamma production by blood mononuclear cells was measured at birth and nine months. Atopy was determined by skin prick tests at age six. Wheezing and non-wheezing LRIs up to age three were diagnosed by a physician. RESULTS: Cord serum IgE levels were similar between all LRI groups and the no LRI group. Children who had wheezing LRIs until the age of three had IgE levels at nine months and at six years within normal ranges for age. In contrast, children who had a non-wheezing LRI before the nine month IgE sample had lower IgE levels at nine months and six years (geometric mean 1.8 IU/ml and 9.9 IU/ml, respectively) compared with children who had no LRIs (3.9 IU/ml and 38.3 IU/ml, respectively). Children who had non-wheezing LRIs after the nine month IgE sample had normal nine month IgE levels (3.2 IU/ml) but decreased IgE levels at six years of age (15.7 IU/ml). Children with more than one non-wheezing LRI before the age of three were less likely to be atopic than those with no LRI (odds radio 0.2). Interferon gamma production was higher in the non-wheezing LRI group at nine months than in the no LRI or wheezing LRI groups. CONCLUSIONS: Non-wheezing LRIs are associated with subsequent depression of IgE levels and reduced skin test reactivity.