Effects of smoking cessation on airflow obstruction and quality of life in asthmatic smokers

Purpose

Smoking elicits airway inflammation and airflow obstruction in patients with asthma, even after smoking cessation. The aim of this study was to examine the effects of smoking cessation on lung function and quality of life (QOL) in asthmatic patients.

Methods

Thirty-two patients with asthma who were active smokers were recruited. After education on the effects of smoking on asthma, 22 patients continued to smoke, and 10 quit smoking. All patients were treated with inhaled fluticasone propionate (1 mg/day) for 3 months. We compared forced expiratory volume in 1 s (FEV1), FEV1/forced vital capacity (FVC), forced expiratory flow between 25 and 75% FVC (FEF_25-75%), and scores on a QOL questionnaire at baseline, 1, 2, and 3 months.

Results

Quitters showed a greater percent change in FEV1 (19.1±6.3 vs. 7.9±2.4%, P=0.024) and FEV1/FVC (6.5±4.14 vs. 3.5±1.5%, P=0.05) than smokers. Both quitters and smokers showed improved QOL scores after 1, 2, and 3 months of fluticasone treatment.

Conclusions

Patients with asthma who quit smoking showed less airway obstruction, suggesting that smoking cessation is crucial in the management of asthma.     

Fractional Exhaled Nitric Oxide and Impulse Oscillometry in Children With Allergic Rhinitis

Purpose

Airway inflammation, bronchial hyper-responsiveness (BHR), and bronchodilator response (BDR) are representative characteristics of asthma. Because allergic rhinitis (AR) is a risk factor for asthma development, we evaluated these 3 characteristics in AR using measurement of fractional exhaled nitric oxide (FeNO), a methacholine challenge test (MCT), and impulse oscillometry (IOS).

Methods

This study included 112 children with asthma (asthma group), 196 children with AR (AR group), and 32 control subjects (control group). We compared pulmonary function parameters and FeNO levels among the 3 groups. The AR group was subdivided into 2 categories: the AR group with BHR and the AR group without, and again pulmonary function and FeNO levels were compared between the 2 subgroups.

Results

FeNO levels were more increased in the AR and asthma groups than in the control group; within the AR group, FeNO was higher in the AR group with BHR than in the AR group without. The BDR was more increased in the AR group than in the control group when percent changes in reactance at 5 Hz (Δ X5) and reactance area (Δ AX) were compared. In the AR group, however, there was no difference in Δ X5 and Δ AX between the AR group with BHR and the AR group without.

Conclusions

Reversible airway obstruction on IOS and elevated FeNO levels were observed in children with AR. Because elevated FeNO levels can indicate airway inflammation and because chronic inflammation may lead to BHR, FeNO levels may be associated with BHR in AR. IOS can be a useful tool for detecting lower airway involvement of AR independent of BHR assessed in the MCT.     

Rhinitis Patients With Sputum Eosinophilia Show Decreased Lung Function in the Absence of Airway Hyperresponsiveness

Purpose

Sputum eosinophilia is observed frequently in patients with rhinitis. Sputum eosinophilia in patients with non-asthmatic allergic rhinitis has been suggested to be related to nonspecific airway hyperresponsiveness (AHR). However, the clinical significance of sputum eosinophilia in patients with non-asthmatic rhinitis without AHR has not been determined. We conducted a retrospective study examining the influence of sputum eosinophilia in patients with non-asthmatic rhinitis without AHR on pulmonary function and expression of fibrosis-related mediators.

Methods

Eighty-nine patients with moderate-to-severe perennial rhinitis without AHR were included. All underwent lung function tests (forced expiratory volume in 1 second [FEV1] and forced vital capacity [FVC]), skin tests to inhalant allergens, methacholine bronchial challenge tests, and hypertonic saline-induced sputum to determine eosinophil counts. Sputum mRNA levels for transforming growth factor-β (TGF-β), matrix metalloproteinase-9 (MMP-9), and tissue inhibitor of metalloproteinase-1 (TIMP-1) were also examined. Patients were divided into two groups according to the presence of sputum eosinophilia (≥3%, eosinophilia-positive [EP] and <3%, eosinophilia-negative [EN] groups).

Results

FEV1 was significantly lower (P=0.04) and FEV1/FVC tended to be lower (P=0.1) in the EP group than in the EN group. In sputum analyses, the MMP-9 mRNA level (P=0.005) and the ratio of MMP-9 to TIMP-1 expression (P=0.01) were significantly higher in the EP group than in the EN group. There was no significant difference in TGF-β mRNA expression between the two groups.

Conclusions

Sputum eosinophilia in patients with moderate-to-severe perennial rhinitis without AHR influenced FEV1 and the expression pattern of fibrosis-related mediators.     

Airway Measurement for Airway Remodeling Defined by Post-Bronchodilator FEV1/FVC in Asthma: Investigation Using Inspiration-Expiration Computed Tomography

Purpose

Airway remodeling may be responsible for irreversible airway obstruction in asthma, and a low post-bronchodilator FEV1/FVC ratio can be used as a noninvasive marker of airway remodeling. We investigated correlations between airway wall indices on computed tomography (CT) and various clinical indices, including post-bronchodilator FEV1/FVC ratio, in patients with asthma.

Methods

Volumetric CT was performed on 22 stable asthma patients who were taking inhaled corticosteroids. Airway dimensions were measured at four segmental bronchi using in-house software based on the full-width/half-maximum method. Parameters included luminal area, wall thickness (WT), wall thickness percentage (WT%), wall area percentage (WA%), bronchial-to-arterial diameter (BA) ratio on inspiration CT, airway collapsibility (AC), and air trapping index (ATI). Correlations were analyzed between CT parameters and clinical indices, including %FEV1, FEV1/FVC, FEF_25-75%, and post-bronchodilator FEV1/FVC ratio.

Results

Post-bronchodilator FEV1/FVC showed significant correlations with WT%, WT, BA ratio, AC, and ATI (r=-0.503, -0.576, 0.454, 0.475, and -0.610, respectively). WT showed negative correlations with FEV1/FVC and FEF_25-75% (r=-0.431 and -0.581), and WT% was negatively correlated with %FEV1, FEV1/FVC, and FEF_25-75% (r=-0.434, -0.431, and -0.540, respectively). WA% showed correlations with FEF_25-75% and body mass index (r=-0.459 and 0.453). The BA ratio was positively correlated with %FEV1 (r=0.459) and FEF_25-75% (r=0.479). AC showed strong positive correlation with FEV1/FVC (r=0.592), and ATI showed negative correlations with FEV1/FVC (r=-0.534) and FEF_25-75% (r=-0.591).

Conclusions

WT%, WT, BA ratio, and AC on inspiration and expiration CT are good indices for measuring airway remodeling defined by post-bronchodilator FEV1/FVC in stable asthma patients treated with inhaled corticosteroids.     

The Burden of Rhinitis and Rhinoconjunctivitis in Adolescents

Purpose

Rhinitis and conjunctivitis are common diseases worldwide that are frequently associated. Nevertheless, the risk factors for rhinoconjunctivitis are not well-described and the impact of conjunctivitis on rhinitis and asthma in children remains unknown. This study explored the different risk factors and evaluated the burden of rhinoconjunctivitis among adolescents.

Methods

This was a cross-sectional study conducted on a random sample of schoolchildren, aged 10-17 years, using skin prick tests and a self-administered questionnaire on respiratory health investigating the impact of rhinitis and rhinoconjunctivitis on daily activities.

Results

A complete evaluation was obtained for 2,150 children. The prevalence of rhinitis alone was 18.2% and rhinitis associated with conjunctivitis was 20.5%. Rhinoconjunctivitis was more frequently associated with females, a parental history of atopy, domestic exposure to mold/dampness, passive smoke exposure, and reported truck traffic in residential streets. Moreover, rhinoconjunctivitis was associated with a higher level of allergic sensitization. The prevalence of current asthma was 1.7% in subjects without rhinitis or rhinoconjunctivitis, 5.1% in rhinitis and 10.7% in rhinoconjunctivitis. In a logistic model, rhinoconjunctivitis yielded a 2-fold risk for current asthma with respect to rhinitis. Subjects with rhinoconjunctivitis had poorer quality of life (QoL); there was an impact on daily activities in 4.6% of rhinitis and 10.7% of rhinoconjunctivitis.

Conclusions

Ocular symptoms increase the role of rhinitis as a risk factor for asthma and its impact on daily activities in children.     

Effect of Traffic-Related Air Pollution on Allergic Disease: Results of the Children's Health and Environmental Research

Purpose

This study evaluated the relationship of living near to main roads to allergic diseases, airway hyperresponsiveness (AHR), allergic sensitization, and lung function in Korean children.

Methods

A total of 5,443 children aged 6-14 years from 33 elementary schools in 10 cities during 2005-2006 were included in a baseline survey of the Children''s Health and Environmental Research. We assessed association of traffic-related air pollution (TAP) exposure with the distance to the nearest main road, total road length of main roads and the proportion of the main road area within the 200-m home area.

Results

Positive exposure-response relationships were found between the length of the main road within the 200-m home area and lifetime wheeze (adjusted prevalence ratio [PR] for comparison of the longest to the shortest length categories=1.24; 95% CIs, 1.04-1.47; P for trend=0.022) and diagnosed asthma (PR=1.42; 95% CIs, 1.08-1.86; P for trend=0.011). Living less than 75 m from the main road was significantly associated with lifetime allergic rhinitis (AR), past-year AR symptoms, diagnosed AR, and treated AR. The distance to the main road (P for trend=0.001), the length of the main road (P for trend=0.041), and the proportion of the main road area (P for trend=0.006) had an exposure-response relationship with allergic sensitization. A strong inverse association was observed between residential proximity to the main load and lung function, especially FEV1, FEV1/FVC, and FEF_25-75. The length of the main road and the proportion of the main road area were associated with reduced FEV1 in schoolchildren.

Conclusions

The results of this study suggest that exposure to traffic-related air pollution may be associated with increased risk of asthma, AR, and allergic sensitization, and with reduced lung function in schoolchildren.     

Influence of Chronic Sinusitis and Nasal Polyp on the Lower Airway of Subjects Without Lower Airway Diseases

Purpose

Upper and lower respiratory tract pathologies are believed to be interrelated; however, the impact of upper airway inflammation on lung function in subjects without lung disease has not been evaluated. This study investigated the association of CT finding suggesting chronic sinusitis and lung function in healthy subjects without lung disease.

Methods

This was a retrospective study of prospectively collected data from 284 subjects who underwent a pulmonary function test, bronchial provocation test, rhinoscopy, and osteomeatal unit computed tomography offered as a private health check-up option.

Results

CT findings showed that the sinusitis group had a significantly lower FEV1/FVC ratio than subjects without sinusitis finding (78.62% vs 84.19%, P=0.019). Among the sinusitis group, subjects classified by CT findings as the extensive disease group had a slightly lower FEV1/FVC than those of the limited disease group (76.6% vs 79.5%, P=0.014) and the associations were independent of the presence of airway hyperresponsiveness. The subjects with nasal polyp had also lower FEV1 and FEV1/FVC than subjects without nasal polyp (FEV1: 100.0% vs 103.6%, P=0.045, FEV1/FVC: 77.4% vs 80.0%, P=0.005).

Conclusions

CT findings suggesting chronic sinusitis and nasal polyp were associated with subclinical lower airway flow limitation even in the absence of underlying lung disease.     

Vitamin D Insufficiency and Asthma Severity in Adults From Costa Rica

Purpose

Non-classical actions of vitamin D as a cytokine are related to the immunopathology of asthma. Few studies have examined vitamin D levels and asthma severity in adults. The aim of this research was to assess the relationship between vitamin D levels, atopy markers, pulmonary function, and asthma severity.

Methods

We analyzed 25-hydroxyvitamin D levels in serum collected from 121 asthmatic adults from Costa Rica to investigate the association between vitamin D levels (categorized as sufficient, ≥30 ng/mL, or insufficient, <30 ng/mL), allergic rhinitis, total IgE and peripheral blood eosinophils (as markers of atopy), asthma severity, baseline forced expiratory volume in 1 second (FEV1), and forced vital capacity (FVC). Univariate and multivariate analyses were performed to assess these relationships.

Results

When the population was stratified by vitamin D status, 91% of asthmatic patients with vitamin D levels below 20 ng/mL (n=36) and 74% of patients with vitamin D levels between 20 and 30 ng/mL (n=73) had severe asthma versus 50% of those with vitamin D sufficiency (n=12; P=0.02). Vitamin D insufficiency was associated with a higher risk of severe asthma (odds ratio [OR], 5.04; 95% Confidence interval [CI], 1.23-20.72; P=0.02). High vitamin D levels were associated with a lower risk of hospitalization or emergency department visit during the last year (OR, 0.90; 95% CI, 0.84-0.98; P=0.04). Although there appeared to be a direct relationship between vitamin D levels and FEV1 (regression coefficient=0.48; r²=0.03), it did not reach statistical significance (P=0.07).

Conclusions

Our findings suggest that vitamin D insufficiency is common among our cohort of asthmatic adults. Lower vitamin D levels are associated with asthma severity.     

Comorbidities in Severe Asthma: Frequency of Rhinitis, Nasal Polyposis, Gastroesophageal Reflux Disease, Vocal Cord Dysfunction and Bronchiectasis

OBJECTIVES

Severe asthma is found in approximately 10% of patients with asthma. Some factors associated with worse asthma control include rhinitis, gastroesophageal reflux disease, vocal cord dysfunction (VCD), nasal polyposis and bronchiectasis. Therefore, we evaluated the prevalence of these illnesses in patients with severe asthma.

METHODS

We conducted a retrospective analysis of data obtained from electronic medical records of patients with severe asthma between January 2006 and June 2008. Symptoms of rhinitis and gastroesophageal reflux disease were evaluated as well as intolerance to nonsteroidal anti-inflammatory drugs. We evaluated the results of esophagogastroduodenoscopy, videolaryngoscopy and CT scans of the chest in order to confirm gastroesophageal reflux disease, nasal polyposis, vocal cord dysfunction and bronchiectasis.

RESULTS

We evaluated 245 patients. Rhinitis symptoms were present in 224 patients (91.4%); 18 (7.3%) had intolerance to nonsteroidal anti-inflammatory drugs, and 8 (3.3%) had nasal polyposis. Symptoms of gastroesophageal reflux disease were reported for 173 (70.6%) patients, although the diagnosis of gastroesophageal reflux disease was confirmed based on esophagogastroduodenoscopy or laryngoscopy findings in just 58 (33.6%) patients. Vocal cord dysfunction was suspected in 16 (6.5%) and confirmed through laryngoscopy in 4 (1.6%). The patient records provided CT scans of the chest for 105 patients, and 26 (24.8%) showed bronchiectasis.

DISCUSSION

Rhinitis and gastroesophageal reflux disease were the most common comorbidities observed, in addition to bronchiectasis. Therefore, in patients with severe asthma, associated diseases should be investigated as the cause of respiratory symptoms and uncontrolled asthma.     

Novel Risk Factors for Allergic Rhinitis in Korean Elementary School Children: ARCO-kids Phase II in a Community

Purpose

Allergic rhinitis (AR) is a multifactorial disease whose genetic and environmental risk factors have been studied for decades. Many pediatric studies have pointed out the familial history of allergy, hygiene hypothesis, breast-feeding, pet ownership, and diets as risk factors of AR. However, most of factors are still up for debate. This preliminary report aimed to confirm the known risk factors and find the novel risk factors for AR in the Korean pediatric population.

Methods

A bi-seasonal, winter and summer, study in 2 elementary schools included all students whose parents completed the questionnaire of medical and social histories, quality of life, infant and early-childhood history, and the living styles. Skin prick tests and endoscopic examinations were conducted on all participants.

Results

Among total 1,020 children, 338 participants had AR. The multivariate logistic regression analysis highlighted 6 factors: male gender (OR, 2.10; 95% CI, 1.32-3.33), older age (1.65; 1.03-2.65), previous history of allergic conjunctivitis (14.25; 4.99-40.74), asthma (2.73; 0.96-7.76) and pneumonia (0.39; 0.19-0.82), and an hour increase in daily playing time (0.90; 0.80-1.00).

Conclusions

Lack of pneumonia in early childhood and short playing time are newly found risk factors for Korean pediatric AR in this study confirming male gender, older age and previous history of allergic conjunctivitis and asthma as the risk factors.     

Clinical Characteristics of Asthma Combined with COPD Feature

Purpose

In clinical practice, some patients with asthma show incompletely reversible airflow obstruction, resembling chronic obstructive pulmonary disease (COPD). The aim of this study was to analyze this overlap phenotype of asthma with COPD feature.

Materials and Methods

A total of 256 patients, over the age of 40 years or more with a diagnosis of asthma, based on either 1) positive response to bronchodilator: >200 mL forced expiratory volume in 1 s (FEV₁) and >12% baseline or 2) positive methacholine or mannitol provocation test, were enrolled. Among the asthma patients, we defined the overlap group with incompletely reversible airflow obstruction [postbronchodilator FEV₁/forced vital capacity (FVC) <70] at the initial time of admission and continuing airflow obstruction after at least 3 months follow up. We evaluated clinical features, serum eosinophil counts, serum total immunoglobulin (Ig) E with allergy skin prick test, spirometry, methacholine or mannitol provocation challenges and bronchodilator responses, based on their retrospective medical record data. All of the tests mentioned above were performed within one week.

Results

The study population was divided into two groups: asthma only (62%, n=159, postbronchodilator FEV₁/FVC ≥70) and overlap group (38%, n=97, postbronchodilator FEV₁/FVC <70). The overlap group was older, and contained more males and a higher percentage of current or ex-smokers than the asthma only group. Significantly lower FEV₁ and higher total lung capacity, functional residual capacity, and residual volume were observed in the overlap group. Finally, significantly lower serum eosinophil count and higher IgE were seen in the overlap group.

Conclusion

Our results showed that the overlap phenotype was older, male asthmatic patients who have a higher lifetime smoking intensity, more atopy and generally worse lung function.     

Assessment of bronchodilator responsiveness following methacholine-induced bronchoconstriction in children with asthma

Purpose

The aim of this study was to investigate bronchodilator responsiveness (BDR) following methacholine-induced bronchoconstriction and to determine differences in BDR according to clinical parameters in children with asthma.

Methods

The methacholine challenge test was performed in 145 children with mild to moderate asthma, and the provocative concentration causing a 20% decline in FEV1 (PC20) was determined. Immediately after the challenge test, patients were asked to inhale short-acting β2-agonists (SABAs) to achieve BDR, which was assessed as the change in FEV1% predicted×100/post-methacholine FEV1% predicted. For each subject, the asthma medication, blood eosinophil count, serum total IgE, serum eosinophil cationic protein level, and skin prick test result were assessed.

Results

The FEV1 (mean±SD) values of the 145 patients were 90.5±10.9% predicted, 64.2±11.5% predicted, and 86.2±11.2% predicted before and after methacholine inhalation, and following the administration of a SABA, respectively. The BDR did not differ significantly according to asthma medication, age, or gender. However, BDR in the atopy group (37.4±17.7%) was significantly higher than that in the non-atopy group (30.5±10.7%; P=0.037). Patients with blood eosinophilia (38.6±18.1%) displayed increased BDR compared with patients without eosinophilia (32.0±13.8%; P=0.037).

Conclusions

In children with mild to moderate asthma, the responsiveness to short-acting bronchodilators after methacholine-induced bronchoconstriction was not related to asthma medication, but was higher in children with atopy and/or peripheral blood eosinophilia.     

Role of angiogenic factors in airway remodeling in an allergic rhinitis murine model

Purpose

There is growing evidence that nasal airway remodeling occurs in allergic rhinitis (AR). Although angiogenesis is an important component of airway remodeling in asthma, its involvement in AR has been little studied. Furthermore, information regarding the role of potent angiogenic factors, such as vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF), in the nasal airway remodeling process is limited. This study was conducted to investigate the role of VEGF and PDGF in nasal airway remodeling, and to assess the preventive effects of anti-angiogenic drugs on this process in a murine AR model.

Methods

Mice were systemically sensitized and subjected to inhalation of ovalbumin (OVA) twice a week for 3 months. Control mice were challenged with phosphate buffered saline, while the treatment group received SU1498, a VEGF receptor inhibitor, and/or AG1296, a PDGF receptor inhibitor, via intraperitoneal injection 4 hours prior to each OVA inhalation. Staining using hematoxylin and eosin, Masson''s trichrome, and periodic acid-Schiff were separately performed to assess eosinophil infiltration, subepithelial fibrosis, and goblet cell hyperplasia, respectively, in the nasal airway. Immunohistochemical staining for matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) was also conducted.

Results

Repetitive intranasal inhalation of OVA resulted in significant increases in eosinophil infiltration, subepithelial fibrosis, goblet cell count, and MMP-9/TIMP-1 expression. Administration of SU1498 or AG1296 prevented these abnormal responses.

Conclusions

The results of this study suggest that a causal relationship may exist between angiogenic factors and nasal airway remodeling in AR. Inhibition of VEGF or PDGF receptors may, in turn, suppress the remodeling process through the regulation of MMP-9/TIMP-1 expression.     

Basement membrane thickening and clinical features of children with asthma

BACKGROUND: Asthma is a chronic inflammatory disease, characterized by airway inflammation, bronchial hyper-responsiveness, and airway obstruction. Although asthma induces partially reversible airway obstruction, obstruction can sometimes become irreversible. This may be a consequence of airway remodeling, which includes a number of structural changes, such as epithelial detachment, basement membrane (BM) thickening, smooth muscle hypertrophy, and new vessel formation. This study evaluated children with asthma for the presence of BM thickening. METHODS: Eighteen children with asthma and 24 control subjects underwent flexible bronchoscopy with endobronchial biopsy. Light microscopy was used to measure BM thickness in paraffin-embedded biopsy sections. The association between BM thickening and age, sex, duration of asthma, asthma severity, FEV(1), FEV(1)/FVC, FEF(25-75%), methacholine PC(20), eosinophil count, and presence of atopy was examined. RESULTS: Basement membrane thickness was greater in subjects with asthma (8.3 +/- 1.4 microM) than in control subjects (6.8 +/- 1.3 microM, P = 0.0008). Multiple regression analysis revealed that sex, FEV(1)/FVC, total IgE, and atopy (IgE for Dermatophagoides pteronyssinus >0.34 kUA/l) were significant predictive factors for BM thickness. There was no significant association between BM thickness and age, duration of asthma, FEV(1), FEF(25-75%), methacholine PC(20), eosinophil count, or asthma severity. CONCLUSIONS: Basement membrane thickening has been known to be present in children with asthma. In addition, we report an association between BM thickness and sex, FEV(1)/FVC, total IgE, and the presence of IgE specific to D. pteronyssinus.     

Lost to Follow-Up in Asthmatics Does Not Mean Treatment Failure: Causes and Clinical Outcomes of Non-Adherence To Outpatient Treatment In Adult Asthma

Purpose

Long-term asthma management is recommended to asthmatics; however, many patients do not adhere to follow-up treatment. It is unclear why many asthmatics do not adhere to follow-up treatment and long-term clinical course after discontinuation of asthma management. This study investigates the factors associated with loss to follow-up and observes the clinical course in asthmatics who discontinued asthma treatment.

Methods

A retrospective investigation was conducted after reviewing medical records of adult patients who were newly diagnosed with asthma at a university hospital in Seoul, South Korea from January 2005 to March 2007. We compared baseline demographics and the clinical and laboratory profiles of patients to see if they successfully adhered to the treatment at an outpatient clinic for at least 3 years. The clinical course and asthma control status were surveyed by telephone for patients who were lost to follow-up within 3 years.

Results

A total of 351 (73.9%) out of 475 patients were lost to follow-up within 3 years of asthma diagnosis. Patients lost to follow-up were younger and had clinical features of less severe asthma at time of diagnosis (higher FEV1 and PC20, and lower grade treatments) compared to patients who adhered to the follow-up for longer than 3 years (all P<0.05). Among the 198 responders to the telephone survey, 124 responders (62.6%) answered that they eventually discontinued asthma medication. A significantly higher proportion of the 124 responders who discontinued asthma treatment maintained symptom improvement compared to the 74 responders who continued asthma medication (77.4% vs. 55.4%, P=0.003).

Conclusions

Almost three quarters of newly diagnosed asthmatics discontinued asthma medication within 3 years despite a medical recommendation. There are considerable numbers of asthmatics who can maintain long-term asthma control status without medication.     

Systemic Inflammation in Older Adults With Asthma-COPD Overlap Syndrome

Purpose

The role of systemic inflammation on asthma-COPD overlap syndrome is unknown. This study aimed to examine systemic inflammation in asthma-COPD overlap syndrome, and to identify associations between clinical characteristics and inflammatory mediators in asthma-COPD overlap syndrome.

Methods

In 108 adults older than 55 years comprising healthy controls (n=29), asthma (n=16), COPD (n=21) and asthma-COPD overlap syndrome (n=42), serum high sensitivity C-reactive protein and Interleukin 6 (IL-6) were assayed. Spirometry, induced sputum, quality of life, comorbidities and medications were assessed, and their associations with asthma-COPD overlap syndrome were analyzed using logistic regression. Associations between systemic inflammatory mediators and clinical characteristics were tested in multivariate linear regression models.

Results

Patients with asthma-COPD overlap syndrome had significantly elevated IL-6 levels compared with healthy controls and asthmatics. Age, comorbidity index and IL-6 level were independently associated with asthma-COPD overlap syndrome. FEV1% predicted was inversely associated with IL-6 level, and cardiovascular disease was associated with an increased IL-6 level. Systemic markers were not associated with airway inflammation.

Conclusions

Systemic inflammation is commonly present in asthma-COPD overlap syndrome, and asthma-COPD overlap syndrome resembled COPD in terms of systemic inflammation. IL-6 is a pivotal inflammatory mediator that may be involved in airflow obstruction and cardiovascular disease and may be an independent treatment target.     

Bronchial Hyperresponsiveness to Methacholine and AMP in Children With Atopic Asthma

Purpose

Bronchial hyperresponsiveness (BHR) is typically measured by bronchial challenge tests that employ direct stimulation by methacholine or indirect stimulation by adenosine 5''-monophosphate (AMP). Some studies have shown that the AMP challenge test provides a better reflection of airway inflammation, but few studies have examined the relationship between the AMP and methacholine challenge tests in children with asthma. We investigated the relationship between AMP and methacholine testing in children and adolescents with atopic asthma.

Methods

The medical records of 130 children with atopic asthma (mean age, 10.63 years) were reviewed retrospectively. Methacholine and AMP test results, spirometry, skin prick test results, and blood tests for inflammatory markers (total IgE, eosinophils [total count, percent of white blood cells]) were analyzed.

Results

The concentration of AMP that induces a 20% decline in forced expiratory volume in 1 second [FEV1] (PC20) of methacholine correlated with the PC20 of AMP (r²=0.189, P<0.001). No significant differences were observed in the levels of inflammatory markers (total eosinophil count, eosinophil percentage, and total IgE) between groups that were positive and negative for BHR to methacholine. However, significant differences in inflammatory markers were observed in groups that were positive and negative for BHR to AMP (log total eosinophil count, P=0.023; log total IgE, P=0.020, eosinophil percentage, P<0.001). In contrast, body mass index (BMI) was significantly different in the methacholine positive and negative groups (P=0.027), but not in the AMP positive and negative groups (P=0.62). The PC20 of methacholine correlated with FEV1, FEV1/forced vital capacity (FVC), and maximum mid-expiratory flow (MMEF) (P=0.001, 0.011, 0.001, respectively), and the PC20 of AMP correlated with FEV1, FEV1/FVC, and MMEF (P=0.008, 0.046, 0.001, respectively).

Conclusions

Our results suggest that the AMP and methacholine challenge test results correlated well with respect to determining BHR. The BHR to AMP more likely implicated airway inflammation in children with atopic asthma. In contrast, the BHR to methacholine was related to BMI.     

Highly significant linkage to chromosome 3q13.31 for rhinitis and related allergic diseases

Background

Allergic diseases such as asthma and rhinitis have closely related phenotypes and often occur with atopy. They show strong familial and intra‐individual clustering, suggesting overlapping disease aetiology. Various loci and candidate genes have been suggested to underlie allergy. Many or all are still inconclusive. Following genome‐wide scans on multiple phenotypes, we previously suggested that chromosome 3q13.12–q21.2 harbours an allergy locus.

Objective

To identify candidate loci in the Danish population, two additional independent sets of sib‐pair families were fine‐scale mapped in candidate regions showing maximum likelihood scores (MLS) ⩾1.5 in the genome‐wide scans.

Results

Twenty eight microsatellite markers in a denser map on chromosome 3q were analysed in 236 allergy sib‐pair families including 125 sib pairs with rhinitis. We report significant evidence for linkage to chromosome 3q13.31 for rhinitis (MLS 5.55, identity by descent (IBD) 63.9%) and atopy (increased specific immunoglobulin E) (MLS 3.71, IBD 61.7%). We obtained an MLS of 5.1 (IBD 67.3%) at 3q13.31 when sib pairs with both rhinitis and atopy were analysed.

Conclusion

This study reports the first statistically significant evidence for a genetic susceptibility locus for rhinitis and to our knowledge shows the most significant evidence to date of linkage for any allergy phenotype.     

Association of Antioxidants With Allergic Rhinitis in Children From Seoul

Purpose

The prevalence of allergic diseases has risen over the last few decades. Many factors, including environmental factors such as those related to diet, have been considered. Among dietary factors, intake of antioxidant-related nutrients has been associated with the risk of allergic disease. We investigated the association of antioxidant nutritional status with allergic rhinitis (AR) in Korean schoolchildren aged 6-12 years.

Methods

Subjects were 4,554 children in Seoul, Korea. The risk of allergic disease was measured using the Korean version of the International Study of Asthma and Allergies in Childhood, and dietary intake was measured by a semi-quantitative food frequency questionnaire. Intake of vitamins A (including retinol and β-carotene), C, and E was used in the analysis.

Results

Vitamin C intake was negatively associated with an increased risk of current symptoms (adjusted odds ratio, 0.886; 95% confidence interval, 0.806-0.973). There was no association between AR and intake of vitamin A, retinol, β-carotene, or vitamin E. Total serum IgE level and sensitization to allergen did not differ according to nutrient intake.

Conclusions

The group of children with increased vitamin C consumption had fewer AR symptoms, despite the lack of a difference in total serum IgE level or allergen sensitization. These findings suggest that nutrient intake, especially that of vitamin C, influences AR symptoms.