Anti-tumor necrosis factor-α antibody treatment reduces pulmonary inflammation and methacholine hyper-responsiveness in a murine asthma model induced by house dust

BACKGROUND/AIMS: Recent studies documented that sensitization and exposure to cockroach allergens significantly increase children's asthma morbidity as well as severity, especially among inner city children. TNF-alpha has been postulated to be a critical mediator directly contributing to the bronchopulmonary inflammation and airway hyper-responsiveness in asthma. This study investigated whether an anti-TNF-alpha antibody would inhibit pulmonary inflammation and methacholine (Mch) hyper-responsiveness in a mouse model of asthma induced by a house dust extract containing both endotoxin and cockroach allergens. METHODS: A house dust sample was extracted with phosphate-buffered saline and then used for immunization and two additional pulmonary challenges of BALB/c mice. Mice were treated with an intravenous injection of anti-TNF-alpha antibody or control antibody 1 h before each pulmonary challenge. RESULTS: In a kinetic study, TNF-alpha levels within the bronchoalveolar lavage (BAL) fluid increased quickly peaking at 2 h while BAL levels of IL-4, IL-5, and IL-13 peaked at later time-points. Mch hyper-responsiveness was measured 24 h after the last challenge, and mice were killed 24 h later. TNF inhibition resulted in an augmentation of these Th2 cytokines. However, the allergic pulmonary inflammation was significantly reduced by anti-TNF-alpha antibody treatment as demonstrated by a substantial reduction in the number of BAL eosinophils, lymphocytes, macrophages, and neutrophils compared with rat IgG-treated mice. Mch hyper-responsiveness was also significantly reduced in anti-TNF-alpha antibody-treated mice and the pulmonary histology was also significantly improved. Inhibition of TNF significantly reduced eotaxin levels within the lung, suggesting a potential mechanism for the beneficial effects. These data indicate that anti-TNF-alpha antibody can reduce the inflammation and pathophysiology of asthma in a murine model of asthma induced by a house dust extract.     

Polyclonal and allergen-induced cytokine responses in adults with asthma: resolution of asthma is associated with normalization of IFN-gamma responses

BACKGROUND: Atopic disease is associated with skewing of immune responses away from a T(H)1 toward a T(H)2 profile. Previous studies have implicated this cytokine imbalance in the development of disease. However, it is not known whether normalization of this imbalance is conversely associated with disease resolution. OBJECTIVE: To further delineate the role of reduced T(H)1 and increased T(H)2 cytokine production in the pathogenesis of atopic disease and to determine whether disease resolution is associated with alteration of cytokine profiles, we investigated cytokine responses in a cohort of adult patients with asthma followed from childhood. METHODS: A cohort of wheezy children and control subjects aged 7 to 10 years were recruited from 1964 to 1967. Subjects were reevaluated every 7 years to monitor the outcome of childhood asthma. At the 42-year follow-up, 89 subjects from this cohort were evaluated for mitogen and house dust mite (HDM)-induced T(H)1 (IFN-gamma) and T(H)2 (IL-4, IL-5, and IL-13) cytokine responses. Cytokine responses were compared in patients with ongoing asthma, patients with resolved asthma, and control subjects. RESULTS: Patients with severe ongoing asthma had significantly reduced HDM-induced IFN-gamma production compared with that of control subjects and patients with resolved asthma. In contrast, HDM-induced IFN-gamma production in patients with resolved asthma was equivalent to that seen in control subjects. Patients with ongoing and resolved asthma produced significantly higher levels of IL-5 in response to HDM compared with that seen in control subjects, with levels being equivalent in patients with active and resolved asthma. HDM-induced IL-13 production was significantly increased in the patients with resolved asthma when compared with that seen in the control subjects. PHA-induced cytokine responses did not parallel HDM-induced responses. CONCLUSION: Patients with persistent and severe atopic asthma have a reduced HDM-induced T(H)1 response, whereas those with resolved asthma do not. This suggests that reduced HDM-induced IFN-gamma production might be an important factor contributing to ongoing severe asthma and that normalization of allergen-induced T(H)1 responses might be important for disease resolution. The finding that all subjects with a history of asthma displayed increased HDM-induced T(H)2 (IL-5 and IL-13) cytokine responses, irrespective of the presence or absence of asthma, suggests that increased T(H)2 responses reflect the presence of the atopic state per se rather than being specifically linked to asthma.     

Reduced airway hyperresponsiveness and tracheal responses during allergic asthma in mice lacking tyrosine kinase inducible T-cell kinase

BACKGROUND: Patients with allergic asthma have symptoms of a predominant T(H)2 response, including airway eosinophilic inflammation and increased mucous production in the lungs. This accompanies increased airways responsiveness, which can be life threatening. Because T(H)2 cells and cytokines have been implicated in contributing to these symptoms, pathways that control the development of these cells or that regulate their cytokine production represent good targets for controlling this disease. OBJECTIVE: We have previously shown that mice lacking the tyrosine kinase inducible T-cell kinase (ITK) have drastically reduced airway inflammation in a model of allergic asthma. However, it was not clear whether this translated into reduced airways hyperresponsiveness. We have analyzed tracheal responsiveness and airways hyperresponsiveness of wild-type (WT) and ITK null mice during induction of experimental allergic asthma. METHODS: Experimental allergic asthma was induced in WT and ITK knockout mice. Tracheal responses to carbachol, acetylcholine, and potassium chloride were analyzed. Airways hyperresponsiveness to methacholine challenge was also analyzed in allergen-challenged mice, along with lung and bronchoalveolar lavage fluid T(H)2 cytokine message and protein. RESULTS: ITK null mice have reduced tracheal responses to cholinergic challenge in vitro before as well as after allergen challenge. These mice also have reduced airways hyperresponsiveness in response to allergen challenge, which could be rescued by transferring WT splenocytes or purified WT CD4+ T cells. This reduced airways response was preferentially accompanied by reduced expression of T(H)2 cytokines in the lungs. CONCLUSION: Our results indicate that the tyrosine kinase ITK and its function in T cells represent an attractive target for antiasthmatic drugs. CLINICAL IMPLICATIONS: Modulating the expression or activity of ITK may be a novel strategy to block allergic airway inflammation.     

Breast-feeding and the prevalence of asthma and wheeze in children: analyses from the Third National Health and Nutrition Examination Survey, 1988-1994

BACKGROUND: Asthma prevalence has increased dramatically in recent years, especially among children. Breast-feeding might protect children against asthma and related conditions (recurrent wheeze), and this protective effect might depend on the duration and exclusivity of the breast-feeding regimen. OBJECTIVE: We sought to determine whether there is an association between breast-feeding and asthma, recurrent wheeze, or both in children up to 72 months of age and whether the duration and exclusivity of breast-feeding affect this association. METHODS: Data were from the third National Health and Nutrition Examination Survey, a nationally representative cross-sectional survey conducted from 1988 to 1994. We tested for significant associations between breast-feeding and physician-diagnosed asthma and recurrent wheeze (> or =3 episodes in the past 12 months) before and after adjusting for potential confounders. RESULTS: Crude analyses showed that breast-feeding was associated with significantly reduced risks for asthma and recurrent wheeze in children 2 to 71 months of age, but after adjusting for potential confounders, these overall protective associations attenuated and were no longer statistically significant. However, 2 new and important associations were revealed after adjusting for confounders: (1) compared with never breast-fed children, ever breast-fed children had significantly reduced odds of being diagnosed with asthma and of having recurrent wheeze before 24 months of age, and (2) among children 2 to 71 months of age who had been exposed to environmental tobacco smoke, those who had ever been breast-fed had significantly reduced risks of asthma and wheeze compared with those who had never been breast-fed. CONCLUSIONS: Breast-feeding might delay the onset of or actively protect children less than 24 months of age against asthma and recurrent wheeze. Breast-feeding might reduce the prevalence of asthma and recurrent wheeze in children exposed to environmental tobacco smoke.     

Asthma in patients with coronavirus disease 2019: A systematic review and meta-analysis

BackgroundIt is unclear whether asthma has an influence on contracting coronavirus disease 2019 (COVID-19) or having worse outcomes from COVID-19 disease.ObjectiveTo explore the prevalence of asthma in patients with COVID-19 and the relationship between asthma and patients with COVID-19 with poor outcomes.MethodsThe pooled prevalence of asthma in patients with COVID-19 and corresponding 95% confidence interval (CI) were estimated. The pooled effect size (ES) was used to evaluate the association between asthma and patients with COVID-19 with poor outcomes.ResultsThe pooled prevalence of asthma in patients with COVID-19 worldwide was 8.3% (95% CI, 7.6-9.0) based on 116 articles (119 studies) with 403,392 cases. The pooled ES based on unadjusted effect estimates revealed that asthma was not associated with reduced risk of poor outcomes in patients with COVID-19 (ES, 0.91; 95% CI, 0.78-1.06). Similarly, the pooled ES based on unadjusted effect estimates revealed that asthma was not associated with the reduced risk of mortality in patients with COVID-19 (ES, 0.88; 95% CI, 0.73-1.05). However, the pooled ES based on adjusted effect estimates indicated that asthma was significantly associated with reduced risk of mortality in patients with COVID-19 (ES 0.80, 95% CI 0.74-0.86).ConclusionThe pooled prevalence of asthma in patients with COVID-19 was similar to that in the general population, and asthma might be an independent protective factor for the death of patients with COVID-19, which suggests that we should pay high attention to patients co-infected asthma and COVID-19 and take locally tailored interventions and treatment. Further well-designed studies with large sample sizes are required to verify our findings.     

Noneosinophilic asthma: a distinct clinical and pathologic phenotype

The use of induced sputum to assess airway inflammation in large and diverse populations with asthma has led to the recognition that significant numbers of patients do not have evidence of eosinophilic airway inflammation. The absence of a sputum eosinophilia has been noted in patients across the range of asthma severity; it has also been reported in patients presenting with an asthma exacerbation. However, whether noneosinophilic asthma represents a pathologically distinct and clinically important asthma phenotype remains unclear. In this review, we present recent evidence suggesting that noneosinophilic asthma represents a stable phenotype associated with a distinct lower airway pathology and structure. We suggest that this lower airway inflammation develops in response to etiologic factors acting through the innate immune pathway and that elements of this immune response contribute to airway dysfunction. Finally, we argue that noneosinophilic asthma is associated with clinically important differences in natural history and treatment response. We particularly highlight evidence that noneosinophilic asthma is associated with a reduced short-term and long-term response to corticosteroid therapy.     

A murine model of toluene diisocyanate–induced asthma can be treated with matrix metalloproteinase inhibitor

BACKGROUND: Toluene diisocyanate (TDI) is a leading cause of occupational asthma. TDI-induced asthma is an inflammatory disease of the airways that is associated with airway remodeling. However, there are little data available on the role of matrix metalloproteinases (MMPs) in TDI-induced asthma. OBJECTIVE: We evaluated whether MMP-9 participates in the airway inflammation in TDI-induced asthma. An additional aim of the present study was to determine whether MMP inhibitors could be effective therapeutic agents for TDI-induced asthma. METHODS: We developed a murine model of TDI-induced asthma to examine the involvement of MMPs by performing 2 sensitizations with 3% TDI and 1 challenge with 1% TDI using ultrasonic nebulization. RESULTS: Murine TDI-induced asthma includes findings of (1) increased inflammatory cells, including neutrophils, lymphocytes, and eosinophils; (2) histologic changes, including infiltration of inflammatory cells around bronchioles, thickened airway epithelium, and accumulation of mucus and debris in the bronchioles; (3) increased MMP-9 activity in inflammatory cells in the airway lumen; and (4) airway hyperresponsiveness. Administration of an MMP inhibitor remarkably reduced all these pathophysiologic findings. CONCLUSION: We conclude that TDI-induced occupational asthma is associated with the induction of MMP-9 in inflammatory cells, and the inhibition of MMP-9 may be a good therapeutic strategy.     

Bronchial responsiveness to leukotriene D4 is resistant to inhaled fluticasone propionate

BACKGROUND: Inhaled corticosteroids are highly effective in asthma, reducing inflammatory markers and bronchial hyperresponsiveness. Cysteinyl-leukotrienes are major mediators of airway obstruction and display proinflammatory effects. Although the synthesis of leukotrienes is not affected by corticosteroid treatment, the influence of corticosteroids on the leukotriene pathway remains unresolved. OBJECTIVE: We investigated whether or not bronchial responsiveness to leukotriene (LT) D(4) is reduced by fluticasone propionate in subjects with asthma. METHODS: In 13 subjects with mild asthma, inhalation challenges with methacholine and LTD(4) were performed on consecutive days before and after 2 weeks of treatment with inhaled fluticasone 500 mug, twice daily, in a double-blind, randomized, placebo-controlled study with crossover design and 3 weeks of washout between periods. Exhaled nitric oxide was measured as a marker of corticosteroid responsiveness, and baseline urinary LTE(4) concentrations as an index of cysteinyl-leukotriene biosynthesis. RESULTS: Fluticasone produced a significant decrease in methacholine responsiveness, corresponding to 2.6-fold shift in the PD(20) FEV(1), and a significant reduction in the levels of exhaled nitric oxide. By contrast, bronchial responsiveness to LTD(4) in the same subjects was unaffected by fluticasone, as were urinary LTE(4) concentrations. CONCLUSION: These new data indicate that neither the biosynthesis nor the actions of leukotrienes appear to be sensitive to inhaled corticosteroids. CLINICAL IMPLICATIONS: The study provides mechanistic support for the additive therapeutic efficacy of antileukotrienes and inhaled corticosteroids in asthma.     

Obesity and asthma: possible mechanisms

Epidemiologic data indicate that obesity increases the prevalence and incidence of asthma and reduces asthma control. Obese mice exhibit innate airway hyperresponsiveness and augmented responses to certain asthma triggers, further supporting a relationship between obesity and asthma. Here I discuss several mechanisms that may explain this relationship. In obesity, lung volume and tidal volume are reduced, events that promote airway narrowing. Obesity also leads to a state of low-grade systemic inflammation that may act on the lung to exacerbate asthma. Obesity-related changes in adipose-derived hormones, including leptin and adiponectin, may participate in these events. Comorbidities of obesity, such as dyslipidemia, gastroesophageal reflux, sleep-disordered breathing, type 2 diabetes, or hypertension may provoke or worsen asthma. Finally, obesity and asthma may share a common etiology, such as common genetics, common in utero conditions, or common predisposing dietary factors. Novel therapeutic strategies for treatment of the obese patient with asthma may result from an increased understanding of the mechanisms underlying this relationship.     

Habituation in neural processing and subjective perception of respiratory sensations

Reduced perception of respiratory sensations is associated with negative treatment outcome in asthma. We examined whether habituation in the neural processing of repeatedly experienced respiratory sensations may underlie subjective reports of reduced respiratory perception. Respiratory-related evoked potentials (RREP) elicited by inspiratory occlusions and reports of respiratory perception were compared between early and late experimental periods in healthy subjects. Reports of respiratory perception were reduced during late, compared to early, experimental periods. This was paralleled by reduced magnitudes in RREP components N1, P2, and P3 in late, compared to early, experimental periods. Habituation in the neural processing of respiratory sensations is a potential mechanism that underlies subjective reports of reduced respiratory perception and might represent a risk factor for reduced perception of respiratory sensations in asthma.     

A case–control study of dietary and erythrocyte membrane fatty acids in asthma

Background Epidemiological evidence suggests that increased dietary ω‐6 and reduced ω‐3 fatty acid intake, may have contributed to the rising prevalence of asthma, but these hypotheses have not been tested in studies comparing both dietary intake and objective measures of polyunsaturated fatty acids. Objective To assess whether a higher intake of ω‐6 or a lower intake of ω‐3 fatty acids increases the risk of asthma, by measuring dietary fatty acid intake by a food frequency questionnaire (FFQ) and erythrocyte membrane fatty acids, as an objective biomarker of intake. Methods We have compared individual fatty acid intake estimated by FFQ and by mass spectrometry of fasting erythrocyte cell membranes in 89 cases of asthma and 89 community‐matched controls. Results The odds of asthma were increased in relation to intake of the ω‐3 fatty acids eicosapentaenoic acid (odds ratio (OR) for difference between the 25th and 75th centiles of intake=1.89, 95% CI 1.15–3.11) and docosahexaenoic acid (OR=2.11, 95% CI 1.19–3.74). There was no evidence of any difference in erythrocyte membrane levels of ω‐3 fatty acids, while the odds of asthma were reduced in relation to linoleic acid (ω‐6) membrane levels (OR=0.45, 95% CI 0.21–0.95). Conclusion These findings suggest that dietary ω‐3 fatty acids do not play a major role in protecting against asthma, and that higher levels of erythrocyte membrane linoleic acid are associated with a lower risk of asthma.     

The inflammatory response in asthma exacerbation: changes in circulating eosinophils, basophils and their progenitors

Circulating eosinophils, basophils and eosinophil/basophil (Eo/B) progenitors were examined in 12 patients at the time of an exacerbation of asthma accompanied by sputum eosinophilia and after resolution of the exacerbation with inhaled corticosteroid treatment. Differential counts were performed and peripheral blood non-adherent mononuclear cells were cultured for 14 days in methyl-cellulose to determine the number of Eo/B and granulocyte-macrophage (GM) colonies without knowledge of the clinical conditions or findings. With resolution of the asthma exacerbation on beclomethasone therapy, there were significant falls in circulating eosinophils, basophils and Eo/B colonies whereas GM colonies were unchanged. To elucidate whether the observed changes could be due to systemic absorption or local action of inhaled corticosteroid, seven subjects with allergic rhinitis and no current evidence of lower airway inflammation (no symptoms of asthma and normal methacholine airway responsiveness) received 14 days' treatment with the same dose of inhaled beclomethasone or of placebo in a double-blind randomized cross-over study. No significant changes in airway function or in circulating cell counts were observed. The results suggest reduced production of eosinophils and basophils after the resolution of an exacerbation of asthma. This effect may be due to reduced levels of airway-derived eosinophil-basophil growth and differentiation factors.     

Effect of Interleukin-8 and Monocyte Chemotactic Protein-1 on Adhesion of Circulating Granulocytes and Monocytes from Asthma Patients to Human Venous Endothelial Cells

The adhesive interactions between phagocytes and endothelial cells (EC) can be modulated by inflammatory cytokines and chemotactic proteins which are released during an inflammatory response. The aim of the present study was to investigate first whether the adhesive properties of granulocytes and monocytes from asthma patients for vascular endothelial cells differ from those of phagocytes from healthy individuals. Furthermore, we studied whether the chemokines interleukin-8 (IL-8) and monocyte chemotactic protein-1 (MCP-1) can affect the binding of phagocytes to EC. No differences were observed in binding of phagocytes from asymptomatic or symptomatic asthma patients and from healthy individuals to non-stimulated or cytokine-stimulated EC. Incubation of granulocytes with IL-8 did not influence their adhesion to non-stimulated EC but inhibited the adhesion of granulocytes to IL-1-stimulated EC. Incubation of monocytes with MCP-1 did not affect their adhesion to non-stimulated or cytokine-stimulated EC. Our results indicate that adhesion of phagocytes to EC depends on the activation state of the endothelial cells but not on the origin of the phagocytes, since there were no differences in the adhesion of phagocytes from asthma patients and healthy individuals to non-stimulated or cytokine-stimulated EC.     

RS Virus-Induced Inflammation and the Intracellular Glutathione Redox State in Cultured Human Airway Epithelial Cells

There is ample evidence that asthma is mediated by oxidative stress and that viral infection, which is associated with asthma onset and exacerbation in infants, acts as one type of oxidative stress. The goal of this study was to determine whether respiratory syncytial virus (RSV) induces oxidative stress in cultured A549 human airway epithelial cells and normal human bronchial epithelial cells (NHBE), and whether such RSV-induced oxidative stress can induce airway inflammation. To evaluate the direct effect of RSV infection as an oxidative stressor, the intracellular levels of reduced glutathione (GSH) or oxidized glutathione (GSSG) were measured. Their ratio (GSH/GSSG) was calculated to indicate intracellular oxidation–reduction (redox) status in A549 and NHBE. To evaluate the extent to which glutathione redox regulation affected cytokine/chemokine production, the effect of pretreatment with a reductive agent, glutathione monoethyl ester (GSH-OEt) and RSV-specific monoclonal antibody was thus studied. RSV acted as a potent oxidative stressor on the intracellular glutathione redox state in human airway epithelial cells, activating signals to increase the production of cytokine/chemokine. Pretreatment with GSH-OEt significantly suppressed RSV-induced time-dependent changes in the intracellular redox state, and also suppressed RSV-induced up-regulation of epithelial cell-derived IL-8, IL-6 and eotaxin production, as well as RSV-specific monoclonal antibody. RSV-induced oxidative stress is likely to contribute to the perpetuation and amplification of the inflammatory response. Therapeutic intervention against oxidative stress might therefore be beneficial as adjunctive therapies for respiratory disorders that are caused by an RSV infection.     

Oral magnesium and vitamin C supplements in asthma: a parallel group randomized placebo-controlled trial

BACKGROUND: Epidemiological studies suggest that higher intakes of dietary vitamin C and magnesium may be associated with a reduced risk of asthma. OBJECTIVE: To determine whether vitamin C or magnesium supplements improve the clinical control of asthma in primary care patients. METHODS: A randomized, placebo-controlled, double-blind parallel group trial of 16 weeks supplementation with 1 g/day vitamin C, 450 mg/day magnesium chelate or matched placebo. Three hundred patients aged 18-60 years with physician-diagnosed asthma, controlled with at least one dose of an inhaled corticosteroid daily, were recruited from 24 primary care practices in Nottingham, UK. The main outcome measures were change in forced expiratory volume in 1 s, forced vital capacity, airway responsiveness to methacholine, mean morning and evening peak flow, symptom scores and bronchodilator use, both individually and as a combined summary statistic. RESULTS: There was no evidence of any beneficial effect of either supplement on any outcome measure of asthma control in the primary intention-to-treat analysis, or in an analysis restricted to participants who completed the study. CONCLUSIONS: Regular dietary supplementation with vitamin C or magnesium adds no clinical benefit to current standard therapy of asthma in primary care patients.     

The role of the C-C chemokine receptor-5 Delta32 polymorphism in asthma and in the production of regulated on activation, normal T cells expressed and secreted.

BACKGROUND: There are conflicting data regarding the role of a deletion in the C-C chemokine receptor-5 gene (CCR5*D32) in the pathogenesis of asthma and whether this deletion influences the production of regulated on activation, normal T cells expressed and secreted (RANTES). RANTES is a chemokine that is known to play an important role in the pathogenesis of allergic asthma. OBJECTIVE: We sought to determine whether CCR5*D32 is associated with increased RANTES production, the presence of asthma, and the severity of asthma. METHODS: A PCR assay for CCR5*D32 was developed. The prevalence of CCR5*D32 was determined in a group of patients with mild-to-moderate asthma, a group of subjects with severe asthma who had fatal or near-fatal asthma attacks, and a group of nonasthmatic control subjects. The level of RANTES produced by stimulated and unstimulated T cells was measured by using a commercially available immunoassay. RESULTS: The frequency of CCR5*D32 was not significantly increased in the severe asthma group compared with in the mild-to-moderate asthma group. CCR5*D32 was not increased in the asthmatic subjects versus in the control subjects. There was no significant increase in RANTES levels from T cells heterozygous for CCR5*D32 compared with wild-type cells. CONCLUSION: These data indicate that the CCR5*D32 allele is not a genetic risk factor for the development of asthma and does not influence disease severity. The CCR5*D32 allele does not influence RANTES production in the heterozygous state.     

High-fat feeding redirects cytokine responses and decreases allergic airway eosinophilia

Background Dietary fat intake has been associated with obesity and obesity in its turn with attenuated airway function and asthma, but it is unclear whether or how high-fat intake per se alters immune function relevant to development of allergic asthma.
Objective To use a non-obese mouse model of mild to moderate allergic asthma to compare effects of high-fat with isocaloric control-diet on allergic immune responses.
Methods C57BL/6 mice weaned and maintained on control (11% fat calories) or isocaloric high-fat diet (58% fat calories) were systemically sensitized with ovalbumin and challenged in the lungs. Allergic airway inflammation was assessed by measuring lung inflammation; serum antibodies; and, cytokines in serum, bronchoalveolar lavage (BAL) fluid and in supernatants of in vitro stimulated lung draining lymph node and spleen lymphocytes.
Results There was a significant reduction in lung eosinophilia and IL-5 in high-fat fed mice. Lung draining lymph node cells from these mice showed reduced pro-inflammatory cytokine (MCP-1 and TNF-α) release after ovalbumin re-stimulation and reduced release of IL-13 after concanavalin-A stimulation, indicating a general rather than just an antigen-specific change. There was no difference in IFN-γ release. In contrast, pro-inflammatory cytokine release was increased from splenocytes. Decreased eosinophilia was not due to increased regulatory T cell or IL-10 induction in draining lymph nodes or spleen, nor to changes in antibody response to ovalbumin. However, decreased levels of serum and BAL eotaxin were found in high-fat fed animals.
Conclusions The data indicate that high-fat dietary content redirects local immune responses to allergen in the lungs and systemic responses in the spleen and serum. These effects are not due to changes in regulatory T cell populations but may reflect a failure to mobilize eosinophils in response to allergic challenge.     

Clinical features of Chlamydia pneumoniae acute respiratory infection

Chlamydia pneumoniae is a worldwide respiratory pathogen involved in 6–20% of community-acquired pneumonias and in about 5% of acute exacerbations of chronic bronchitis. Preliminary data also indicate a possible association between Chlamydia pneumoniae infection and asthma. Further studies are needed to elucidate whether Chlamydia pneumoniae is merely a precipitant of asthma symptoms or is actually one of the causes of asthma.