Challenge with environmental tobacco smoke exacerbates allergic airway disease in human beings

BACKGROUND: Despite widespread perceptions that environmental tobacco smoke (ETS) is a potent risk factor for allergic airway disease, epidemiologic studies studying this have been equivocal. There is a clear need for experimental studies to address these questions. OBJECTIVE: We directly tested the hypothesis that ETS could interact with allergen in human beings to alter immune responses and promote changes associated with allergic airway disease. METHODS: In a randomized, placebo-controlled crossover study, 19 nonsmoking volunteers with ragweed allergy underwent nasal lavage followed by controlled chamber exposures to 2 hours ETS or clean air followed by another nasal lavage. Subjects immediately randomly received nasal challenge with either ragweed allergen or placebo (300 microL saline). Lavages were also performed 10 minutes, 24 hours, and 4 and 7 days after challenge and IgE, cytokines, and histamine measured. The other arms of the study were spaced at least 6 weeks apart. RESULTS: Environmental tobacco smoke promoted the production of allergen-specific IgE, the hallmark of allergic disease in nasal lavage fluid. Four days after exposure to ETS/ragweed, levels were on average 16.6-fold higher than after clean air/ragweed challenge. In addition, ETS (vs air) promoted the induction of a T(H)2-cytokine nasal milieu (increased IL-4, IL-5, and IL-13 and decreased IFN-gamma production), characteristic of an active allergic response. Moreover, nasal histamine levels were 3.3-fold greater after ETS/ragweed challenge than after clean air/ragweed challenge. CONCLUSION: These studies provide the first experimental evidence that secondhand smoke can exacerbate allergic responses in human beings. CLINICAL IMPLICATIONS: The studies suggest that patients with allergies should avoid tobacco smoke.     

Smoking exposure and allergic sensitization in children according to maternal allergies.

BACKGROUND: Although the negative impact of environmental tobacco smoke (ETS) on airway diseases in children is well known, the effect of ETS on allergic sensitization is still debated. OBJECTIVE: To evaluate how maternal allergies modulate the effect of tobacco exposure on allergic sensitization in childhood. METHODS: Of 9000 children in grades 4 and 5 selected in 6 cities in France, 7798 participated in a survey that consisted of an epidemiologic questionnaire, skin prick testing to common allergens, and skin examination for eczema. Tobacco exposure was obtained from parent questionnaires. RESULTS: Twenty-five percent of the children had allergic sensitization, 25.2% had eczema, 11.6% had allergic rhinitis, 9.9% had asthma, and 8.3% had exercise-induced asthma. Twenty percent of the children were exposed to tobacco in utero. Maternal exposure had a greater impact than paternal exposure on children's allergic sensitization. Prenatal exposure was more associated with sensitization than postnatal exposure. Children with maternal allergies and exposure to maternal ETS during pregnancy were at higher risk for sensitization to house dust mite (25.7% vs. 14.0%; odds ratio, 1.95; 95% confidence interval, 1.19-3.18; P = .006). In contrast, sensitization to food allergens was not associated with tobacco exposure. CONCLUSIONS: Children exposed to maternal smoking had a higher risk of sensitization to house dust mite, especially when the mothers were allergic.     

Analysis of Ig subclass deficiency: First reported case of IgG2, IgG4, and IgA deficiency caused by deletion of C alpha 1, psi C gamma, C gamma 2, C gamma 4, and C epsilon in a Mongoloid patient

BACKGROUND: IL-4 and IL-13 have been shown to be critical for expression of the asthma phenotype in a murine model and may modulate human fibroblast function. OBJECTIVE: We hypothesized that IL-4 and IL-13 would increase airway fibroblast proliferation and reduce the ability of dexamethasone to decrease this proliferation. METHODS: Six subjects with severe asthma, 5 subjects with mild asthma, and 5 healthy subjects underwent bronchoscopy with endobronchial biopsy. Biopsy specimens were placed in Dulbecco modified Eagle medium and cultured, and only fibro-blasts from the first and second passages were evaluated. Cells were incubated with IL-4 (50 ng/mL), IL-13 (10 ng/mL), and the combination for 48 hours in the presence and absence of dexamethasone, 10(-7) mol/L, and 10(-8) mol/L. Fibroblasts were also incubated with IFN-gamma at 50 ng/mL to assess the response of a T(H)1 cytokine on proliferation. RESULTS: Fibroblast proliferation, determined by (3)H-thymidine incorporation, was significantly increased by IL-4 in subjects with mild asthma as compared with IL-4 in subjects with severe asthma and healthy subjects (P =.003), IL-13 (P =.011), and the combination (P =.004). Dexamethasone also increased proliferation in the group with mild asthma as compared with the group with severe asthma and the healthy group (10(-7) mol/L, P =.02; 10(-8) mol/L, P =.02). IFN-gamma did not significantly alter airway fibroblast proliferation. CONCLUSION: IL-4, IL-13, and dexamethasone all significantly increased fibroblast proliferation in subjects with mild asthma.     

Second-hand smoke increases bronchial hyperreactivity and eosinophilia in a murine model of allergic aspergillosis

Involuntary inhalation of tobacco smoke has been shown to aggravate the allergic response. Antibodies to fungal antigens such as Aspergillus fumigatus (Af) cause an allergic lung disease in humans. This study was carried out to determine the effect of environmental tobacco smoke (ETS) on a murine model of allergic bronchopulmonary aspergillosis (ABPA). BALB/c mice were exposed to aged and diluted sidestream cigarette smoke to simulate 'second-hand smoke'. The concentration was consistent with that achieved in enclosed public areas or households where multiple people smoke. During exposure, mice were sensitized to Af antigen intranasally. Mice that were sensitized to Af antigen and exposed to ETS developed significantly greater airway hyperreactivity than did mice similarly sensitized to Af but housed in ambient air. The effective concentration of aerosolized acetylcholine needed to double pulmonary flow resistance was significantly lower in Af + ETS mice compared to the Af + AIR mice. Immunological data that supports this exacerbation of airway hyperresponsiveness being mediated by an enhanced type 1 hypersensitivity response include: eosinophilia in peripheral blood and lung sections. All Af sensitized mice produced elevated levels of IL4, IL5 and IL10 but no IFN-gamma indicating a polarized Th2 response. Thus, ETS can cause exacerbation of asthma in ABPA as demonstrated by functional airway hyperresponsiveness and elevated levels of blood eosinophilia.     

Soluble interleukin-2 receptor and interleukin-4 in sera of asthmatic children before and after a prednisolone course.

BACKGROUND: Cytokine-mediated interactions among inflammatory cells may play a role in the pathogenesis of bronchial asthma. OBJECTIVE: To understand the role of soluble interleukin-2 receptor (sIL-2R) and interleukin-4 (IL-4) in the disease activity of acute asthma, changes in serum concentrations of sIL-2R and IL-4 elaborated by activated T-lymphocyte before and after prednisolone therapy with clinical improvement were determined in the present study. METHODS: Circulating levels of sIL-2R and IL-4 in sera from 15 normal control subjects and in sera from 20 allergic asthmatic children with acute exacerbation and in a stable condition were determined by using commercially available ELISA kits. RESULTS: The mean concentration of serum sIL-2R was significantly higher in acute exacerbation than in children with stable asthma (368.9 +/- 395.4 pg/mL vs 291.2 +/- 361.0 pg/mL; P < .01) or in control subjects (124.6 +/- 17.8 pg/mL; P < .001). The mean concentration of serum IL-4 was higher in acute exacerbation (5.82 +/- 1.10 pg/mL) and in stable asthmatic patients (6.73 +/- 2.83 pg/mL) versus control group subjects (5.54 +/- 1.20 pg/mL). However, the difference was not statistically significant among the three study groups. CONCLUSIONS: This study provides further evidence that changes in serum IL-2R may serve as an objective indicator for clinical outcome of allergic asthmatic patients.     

Environmental Tobacco Smoke and Progesterone Alter Lung Inflammation and Mucous Metaplasia in a Mouse Model of Allergic Airway Disease

The prevalence and severity of asthma is sexually dimorphic. Adult women have a higher incidence of asthma than men. This suggests that this disease may have a hormonal component. Progesterone has been shown to elicit an immune response similar to that seen in allergic asthma and previous studies have shown that progesterone increases total IgE levels in the peripheral blood. In the current study, we examine the effect of environmental tobacco smoke (ETS) and progesterone on hallmarks of asthma pathology in lung tissue with the goal of defining whether progesterone can also exacerbate two key features of airway remodeling: accumulation of eosinophils and increased mucous. We used a mouse model of allergic asthma that includes house dust mite allergen (HDMA). Adult female BALB/c mice were ovariectomized and implanted with time-release progesterone pellets. Mice were housed in filtered air or ETS for 6 weeks (1 mg/m3 total suspended particulate) and exposed to HDMA by inhalation. Progesterone alone did not increase mucous cell mass or the abundance of eosinophils but ETS coupled with progesterone exposure resulted in a significant increase in mucous cell metaplasia and increased accumulation of eosinophils in the asthma model. Levels of cytokines in the bronchoalveolar lavage fluid, measured using a multiplex cytokine assay, revealed elevated levels of both interleukin (IL)-5 and IL-12(p40) in HDMA-exposed animals. The addition of progesterone further exacerbated this response. We conclude that progesterone, in the absence of estrogen, exacerbates airway inflammation and airway remodeling induced by the toxicant ETS.     

Leukotrienes and 8-isoprostane in exhaled breath condensate of children with stable and unstable asthma

BACKGROUND: Cysteinyl-leukotrienes (cys-LTs) and 8-isoprostane are biomarkers of airway inflammation and oxidative stress. OBJECTIVE: The aim of this study was to evaluate cys-LT and 8-isoprostane levels in exhaled breath condensate (EBC) of children with different degrees of asthma severity. METHODS: EBC was collected from 14 steroid-naive children with mild persistent asthma, 13 children with stable mild- to-moderate persistent asthma treated with inhaled corticosteroids (ICS), 9 ICS-treated children with unstable asthma, and 19 healthy children. RESULTS: In the three groups of asthmatic children, EBC concentrations of cys-LTs and 8-isoprostane were significantly higher than in control children (steroid-naive asthmatic children: cys-LTs median, 10.8 pg/mL, P <.001, 8-isoprostane, 16.2 pg/mL, P <.001; ICS-treated stable asthmatic children: cys-LTs, 12.7 pg/mL, P <.001, 8-isoprostane, 18.1 pg/mL, P <.001; children with unstable asthma: cys-LTs, 106.0 pg/mL, P <.01, 8-isoprostane, 29.7 pg/mL, P <.01; control children: cys-LTs, 4.3 pg/mL, 8-isoprostane, 3.5 pg/mL). Cys-LT levels were higher in children with unstable asthma than in the other two asthmatic groups (P <.05). FE(NO) levels were significantly higher in steroid-naive and in children with unstable asthma compared with ICS-treated children with stable asthma (P <.01). CONCLUSIONS: Our study shows that EBC cys-LTs and 8-isoprostane concentrations are higher in asthmatic children than in healthy control children, with scattered values in patients with unstable asthma. These findings suggest that EBC eicosanoid measurement may have useful clinical implications for investigating phenotype differences among asthmatic patients.     

Association between environmental tobacco smoke and diminished dendritic cell interleukin 10 production during infancy.

BACKGROUND: Diminished interleukin 10 (IL-10) production has been documented in children and adults with asthma and atopy. Environmental tobacco smoke (ETS) is recognized as a risk factor for the development of childhood asthma. OBJECTIVE: To determine whether there is an association between ETS and dendric cell (DC) IL-10 production during infancy. METHODS: ETS was evaluated by questionnaire, and blood samples were obtained at 2 weeks, 3 months, and 5 months of age in 37 healthy infants. DCs were cultured and stimulated, and supernatants were assayed for IL-10 by enzyme immunoassay. RESULTS: Sixteen infants had no history of exposure to ETS, and 21 infants had a history of ETS exposure. The frequency of subjects with detectable IL-10 levels was similar in both groups at 2 weeks and 3 months but significantly different at 5 months (P < .001). In those without ETS exposure, the frequency with detectable IL-10 levels increased during the observation period (25% at 2 weeks, 20% at 3 months, and 36% at 5 months; P = .03 vs 2 weeks). In contrast, in those with ETS exposure, the frequency with detectable IL-10 levels decreased during the observation period (33% at 2 weeks, 19% at 3 months; P = .02 vs 2 weeks; and 7% at 5 months; P < .001 vs 2 weeks). CONCLUSIONS: Our study results demonstrate an association between ETS and diminished DC IL-10 production during infancy. Future studies need to expand on these sample sizes and explore whether diminished DC IL-10 production is the mechanism by which ETS predisposes patients to the development of asthma and/or atopy.     

Prenatal environmental tobacco smoke exposure increases allergic asthma risk with methylation changes in mice

Allergic asthma remains an inadequately understood disease. In utero exposure to environmental tobacco smoke (ETS) has been identified as an environmental exposure that can increase an individual's asthma risk. To improve our understanding of asthma onset and development, we examined the effect of in utero ETS exposure on allergic disease susceptibility in an asthmatic phenotype using a house dust mite (HDM) allergen‐induced murine model. Pregnant C57BL/6 mice were exposed to either filtered air or ETS during gestation, and their offspring were further exposed to HDM at 6–7 weeks old to induce allergic inflammation. Methylation in the promoter regions of allergic inflammation‐related genes and genomic DNA was quantified. Exposure to HDM resulted in the onset of allergic lung inflammation, with an increased presence of inflammatory cells, Th2 cytokines (IL‐4, IL‐5, and IL‐13), and airway remodeling. These asthmatic phenotypes were significantly enhanced when the mice had been exposed to in utero ETS. Furthermore, prenatal ETS exposure and subsequent HDM (ETS/HDM)‐induced asthmatic phenotypes agree with methylation changes in the selected asthma‐related genes, including IL‐4, IL‐5, IL‐13, INF‐γ, and FOXP3. Global DNA methylation was significantly lower in ETS/HDM‐exposed mice than that of controls, which coincides with the results observed in lung, spleen, and blood DNAs. Prenatal ETS exposure resulted in a severe increase in allergic inflammatory responses after an HDM challenge, with corresponding methylation changes. Prenatal ETS exposure may influence developmental plasticity and result in altered epigenetic programming, leading to an increased susceptibility to asthma. Environ. Mol. Mutagen. 58:423–433, 2017. © 2017 Wiley Periodicals, Inc.     

Intranasal steroid reduces exhaled bronchial cysteinyl leukotrienes in allergic patients

BACKGROUND: Allergic rhinitis (AR) precedes and is often associated with bronchial asthma. Indeed, local and systemic inflammations in both conditions are very similar. Cysteinyl-leukotrienes (cys-LTs) are generated during early- and late-phase allergic reactions and induce smooth-muscle contraction, microvascular leakage, and mucous hypersecretion. Cys-LTs are detected in exhaled breath condensate (EBC) of asthmatics and regardless of bronchial symptoms, they are also found in EBC of rhinitic patients. OBJECTIVE: To evaluate cys-LTs in EBC of allergic patients and to assess the activity of nasal fluticasone propionate (FP) on EBC cys-LTs levels. METHODS: Cys-LTs coefficient of variation (CV) was evaluated from different EBC in 5 healthy volunteers. Cys-LTs levels from EBCs in 13 healthy controls and 56 allergic rhinitic (n=31) and rhinitic/asthmatic (n=25) patients were also evaluated at baseline. Subsequently patients were randomized to receive either FP 100 microg/day per nostril or placebo for 2 weeks and then re-evaluated for EBC cys-LTs. RESULTS: The CV was 14.12%. EBC cys-LTs in allergic patients were significantly higher than in healthy subjects (70.9 vs. 20.6 pg/mL (median), P<0.05), while it did not differ between asthmatic/rhinitic and purely rhinitic patients. Treatment significantly reduced cys-LTs (from 93.6 to 19.9 pg/mL, P<0.001). This effect was evident both in asthmatic/rhinitic and in rhinitic patients. CONCLUSION: Treatment of AR with FP significantly reduces the levels of cys-LTs, major noninvasive markers of lower airway inflammation, suggesting that upper and lower airway inflammation is present and should be thus treated as a whole in subjects with AR with and without asthma.     

Squamous cell carcinoma-related antigen in children with acute asthma.

BACKGROUND: Increased serum levels of squamous cell carcinoma-related antigen (SCCA) have been observed in patients with allergic disorders, such as atopic dermatitis and bronchial asthma. T(H)2 cytokines, which are known to be involved in the pathogenesis of allergic disorders, stimulate new synthesis of SCCA in cultured human airway epithelial cells. OBJECTIVE: To investigate whether SCCA levels increase during acute exacerbations of asthma in children and whether the T(H)2 cytokines, interleukin 4 (IL-4) and IL-13, are associated with SCCA levels. METHODS: Serum levels of SCCA, IL-4, and IL-13 were measured by enzyme immunoassay during the acute phase of an asthma exacerbation (on hospital admission) and in the recovery phase (after symptoms had subsided). RESULTS: In the 35 children who participated in this study, serum levels of SCCA were significantly elevated in the acute phase (mean +/- SD, 3.09 +/- 2.03 ng/mL) compared with the recovery phase (mean +/- SD, 1.47 +/- 0.64 ng/mL) of an asthma exacerbation (P < .001). In 12 children, the IL-13 levels were observed to correlate with SCCA levels during the recovery phase (r = 0.68, P = .02) but not during the acute phase of an asthma exacerbation. CONCLUSIONS: Serum SCCA levels increase during the acute phase of an asthma exacerbation. During this phase, the increased synthesis of SCCA is not associated with IL-13 but rather mediated by other undefined stimuli. IL-13 may contribute to the basal production of SCCA in asthmatic children.     

Progesterone and environmental tobacco smoke act synergistically to exacerbate the development of allergic asthma in a mouse model

BACKGROUND: Asthma affects males and females differently. Females have a higher incidence than males after the onset of puberty. This suggests a hormonal component to the development of the disease. Progesterone, a female hormone, has previously been shown to illicit a T-helper type 2 (TH2) immune response similar to that seen in allergic asthma. Previous studies performed by our laboratory have shown that exposure to environmental tobacco smoke (ETS) enhances the immune response to allergens. OBJECTIVE: To determine if the combination of exposure to ETS and progesterone would further exacerbate the immune response in a mouse model of allergic asthma. METHODS: Female mice were ovariectomized and then implanted with time-release progesterone pellets. Mice were housed in either filtered air (FA) or ETS chambers and half were exposed to aerosolized house dust mite allergen (HDMA). Bronchoalveolar lavage was performed for cell differentials; lung and spleen cells were harvested to compare IL-4 and IFN-gamma production by ELISPOT. RESULTS: Progesterone pellet implantation resulted in increased serum progesterone levels (28.3+/-8.43 vs. 13.5+/-7.22 ng/mL in placebo-treated mice, P<0.0001). Serum total IgE levels were significantly greater in progesterone vs. non-progesterone treated animals that were also exposed to HDMA. ETS exposure enhanced total IgE levels as well. Lung homogenate cells from HDMA/progesterone-treated animals stimulated with Concavalin A produced significantly more IL-4 compared with HDMA/placebo-treated animals (200+/-17.6 vs. 146+/-17.5 spots/well, P<0.01 in ETS exposed animals and 221+/-28.9 vs. 167+/-23.4 spots/well, P<0.01 in animals housed in FA). HDMA/ETS-treated animals had higher eosinophilia in lavage than all other groups. CONCLUSION: Increased serum progesterone levels exacerbate the allergic asthmatic phenotype in a mouse model. These effects are further exacerbated by the addition of environmental tobacco smoke. Progesterone provides a major contribution to the gender differences seen in the development and elicitation of the asthmatic response.     

Passive cigarette smoke-challenge studies: increase in bronchial hyperreactivity.

Degree and duration of bronchial hyperreactivity (BHR) after environmental tobacco smoke (ETS) inhalation was assessed in 31 smoke-sensitive subjects with asthma who exhibited lower airway symptoms on ETS exposure (group I) and 39 smoke-sensitive subjects without asthma who manifested only upper airway symptoms on cigarette-smoke exposure (group II). Subjects were challenged with ETS for 4 hours in a static-test chamber. The atmosphere was continuously monitored for airborne particulate levels (800 cpm), total suspended particulates (1266 +/- 283 micrograms/m3), and airborne nicotine levels (226 +/- 49 micrograms/m2). Methacholine challenges were performed before and serially after cigarette-smoke exposure, and the provocative dose causing a 20% fall in FEV1 was determined. Five of the 31 smoke-sensitive subjects with asthma and none of the smoke-sensitive subjects without asthma reacted to cigarette-smoke challenge (greater than or equal to 20% fall from baseline FEV1). Thirty-two percent (10/31) of the subjects with asthma demonstrated increased BHR at 6 hours, 29% (9/31) at 24 hours, and 13% (4/31) up to day 14 after ETS challenge. Of the subjects without asthma, 18% (7/39) demonstrated increased BHR at 6 hours, 10% (4/39) at 24 hours, and 8% (3/39) at 3 weeks. These studies demonstrated an increase in BHR after cigarette-smoke challenge in a number of study subjects (although they were clinically asymptomatic) and suggest that prolonged subclinical airway inflammation can occur in the absence of demonstrable change in airway caliber on exposure to ETS.     

过敏性紫癜患儿血清IL-9、IL-17、MMP-13的变化及意义

目的:探讨过敏性紫癜患儿血清白细胞介素-9(interleukin,IL)-9、IL-17、基质金属蛋白酶-13(metalloproteinase-13,MMP-13)的变化以及临床意义。方法:选取2016年9月至2018年9月于滨州医学院附属医院儿科收治的122例过敏性紫癜患儿作为实验组,随机选取50例健康儿童作为...     

Dissecting asthma using focused transgenic modeling and functional genomics

BACKGROUND: Asthma functional genomics studies are challenging because it is difficult to relate gene expression changes to specific disease mechanisms or pathophysiologic features. Use of simplified model systems might help to address this problem. One such model is the IL-13/Epi (IL-13-overexpressing transgenic mice with STAT6 expression limited to epithelial cells) focused transgenic mouse, which isolates the effects of a single mediator, IL-13, on a single cell type, the airway epithelial cell. These mice develop airway hyperreactivity and mucus overproduction but not airway inflammation. OBJECTIVE: To identify how effects of IL-13 on airway epithelial cells contribute to gene expression changes in murine asthma models and determine whether similar changes are seen in people with asthma. METHODS: We analyzed gene expression in ovalbumin allergic mice, IL-13-overexpressing mice, and IL-13/Epi mice with microarrays. We analyzed the expression of human orthologues of genes identified in the mouse studies in airway epithelial cells from subjects with asthma and control subjects. RESULTS: In comparison with the other 2 models, IL-13/Epi mice had a remarkably small subset of gene expression changes. Human orthologues of some genes identified as increased in the mouse models were more highly expressed in airway epithelial cells from subjects with asthma than in controls. These included calcium-activated chloride channel 1, 15-lipoxygenase, trefoil factor 2, and intelectin. CONCLUSION: The combination of focused transgenic models, DNA microarray analyses, and translational studies provides a powerful approach for analyzing the contributions of specific mediators and cell types and for focusing attention on a limited number of genes associated with specific pathophysiologic aspects of asthma.     

Do children with asthma and their parents agree on household ETS exposure? Implications for asthma management

The adverse consequences of passive smoking have spurred efforts to reduce environmental tobacco smoke (ETS) exposure among children, particularly in the home. For children with asthma, teaching them to avoid tobacco smoke at home is an important element of patient self-management. This strategy assumes that children can accurately assess household smoking behaviors and the level of their own exposure in the home. This study compared child and parental assessments of household smoking behaviors in an urban, low-income and largely ethnic minority sample of asthmatic children and their parents. While there was general parent-child agreement on the smoking status of household members, there was less agreement on duration of household smoking and the child's exposure to ETS. Objective validation measures (cotinine, nicotine) suggest that parents were better able than their children to assess hours of indoor smoking. Children's assessment of the extent of exposure to ETS may be problematic, with important implications for asthma patient self-management efforts.     

Environmental tobacco smoke exposure and nocturnal symptoms among inner-city children with asthma

BACKGROUND: Environmental tobacco smoke (ETS) is a frequent exposure and is linked to asthma among inner-city children. OBJECTIVE: We sought to examine the relationship among ETS exposure, select asthma symptoms, and consequences among inner-city children with asthma. METHODS: Data from interviews with primary caregivers of inner-city elementary school children with asthma were evaluated (n = 590). Caregiver reports of child asthma symptoms, exercise limitations, asthma management, health care use, and ETS exposure were examined. RESULTS: Smoking in the home was reported by 29.4% of primary caregivers. ETS exposure (yes/no) was not related to frequency of child nocturnal symptoms or other select asthma morbidity markers. However, among children exposed to ETS, the frequency and severity of child nocturnal symptoms were highest among children exposed to moderate-to-heavy levels of ETS. After controlling for child age, anti-inflammatory medication use, asthma primary care, and caregiver's education, exposure to higher levels of ETS was associated with nearly a 3-fold increase in nocturnal symptoms in children (odds ratio, 2.83; 95% CI, 1.22-6.55). CONCLUSION: Among elementary school inner-city children with asthma, exposure to higher levels of ETS was associated with increased frequency of nocturnal symptoms. Reducing the exposure of children with asthma to ETS should be a clear priority in developing effective asthma management plans for inner-city families.     

Elevated serum melatonin is associated with the nocturnal worsening of asthma

BACKGROUND: Increased airway inflammation at night contributes to the nocturnal worsening of asthma. In vitro studies have shown exogenous melatonin to be pro-inflammatory in asthma, but it is unknown whether endogenous melatonin levels are a controller of airway inflammation in nocturnal asthma. OBJECTIVE: Our aim was to determine 24-hour patterns of serum melatonin and their relationship to overnight decline in physiology in subjects with nocturnal asthma, non-nocturnal asthma, and in healthy controls. METHODS: Observational study of pulmonary physiology and melatonin levels in patients with nocturnal asthma (n = 7), non-nocturnal asthma (n = 13), and healthy controls (n = 11). Subjects maintained a constant sleep-wake regimen for 7 days. On day 8, serum melatonin was measured every 2 hours by radioimmunoassay and analyzed by cosinor modeling. The correlation between serum melatonin levels and overnight change in spirometry was evaluated by Spearman's rank correlation analysis. RESULTS: In subjects with nocturnal asthma, peak melatonin levels were significantly elevated compared with healthy controls (67.6 +/- 5.0 pg/mL versus 53.5 +/- 4.0 pg/mL, P =.03). Melatonin acrophase was delayed in nocturnal asthma (02:54 versus 01:58 in healthy controls, P =.003, and 02:15 in non-nocturnal asthma, P =.01). In subjects with nocturnal asthma, increasing melatonin levels were significantly and inversely correlated with overnight change in FEV(1) (r = -.79, P =.04), a relationship that was not observed in non-nocturnal asthma or healthy controls. CONCLUSIONS: Nocturnal asthma is associated with elevation and phase delay of peak serum melatonin levels. Elevated melatonin levels might contribute to the pathogenesis of nocturnal asthma.     

Diminished dendritic cell interleukin 10 production in atopic children.

BACKGROUND: Diminished interleukin 10 (IL-10) and/or IL-12 production may contribute to the pathogenesis of asthma and atopy. Dendritic cells (DCs) produce these cytokines and have been implicated in the pathogenesis of these disorders. OBJECTIVE: To determine whether DC IL-10 and/or IL-12 production is diminished in children aged 6 to 12 years with allergic rhinitis (AR) and with or without asthma. METHODS: Monocyte-derived DCs were isolated from 20 subjects without AR or asthma (group 1), 20 subjects with AR without asthma (group 2), and 20 subjects with AR and asthma (group 3). Asthma was defined as a history of physician-diagnosed disease, and AR was defined as a positive history and positive puncture skin test responses (wheal > or = 5 mm) to relevant inhalant allergens. DCs were stimulated with either lipopolysaccharide (LPS) or diluent and cultured for 24 hours. Supernatants were assayed for IL-10 and IL-12 levels by enzyme-linked immunosorbent assay. RESULTS: DC IL-10 production was diminished in groups 2 and 3 compared with group 1. Median LPS-induced IL-10 levels were 11.0 pg/mL in group 1, 6.1 pg/mL in group 2, and 1.5 pg/mL in group 3. The frequencies of subjects with detectable IL-10 levels were 85%, 20%, and 20% in groups 1, 2 and 3, respectively. Median LPS-induced IL-12 levels were similar in all groups. CONCLUSIONS: These data support the hypothesis that atopic subjects have an intrinsic inability to up-regulate DC IL-10 production. Future studies in this area could lead to a better understanding of the pathogenesis of atopy.