Burden of illness of patients with allergic asthma versus non-allergic asthma

Abstract

Objective: Allergic and non-allergic asthma share similar symptoms, but differ in that allergic asthma is triggered by inhaled allergens. This study compared healthcare resource utilization (HCRU) and costs between these groups using US employer-based claims data. Methods: Health insurance claims from Truven Marketscan database (2002Q1-2010Q2) were analyzed. Included patients had ≥2 asthma diagnoses and ≥1 year of eligibility prior to and following the date of first asthma diagnosis. Patients with ≥1 diagnosis for allergic asthma and ≥1 diagnosis for other allergic conditions formed the allergic asthma cohort whereas patients without any of these diagnoses formed the non-allergic asthma cohort. Allergic and non-allergic asthma patients were matched 1:1. HCRU and costs during the study period were compared between cohorts using incidence rate ratios (IRR) and bootstrap methods. Results: Sixty four thousand four hundred and seventy three allergic and non-allergic asthma patients were matched (mean age?=?30; 57.1% female; mean CCI?=?0.2), with 7.1% and 0.36% having received an allergy test during the baseline period, respectively. During the study period, allergic asthma patients had significantly more asthma-related pharmacy dispensings (IRR[95% CI]?=?2.25[2.22–2.28], p?<?0.001) and asthma-related outpatient visits (IRR[95% CI]?=?2.29[2.27–2.32], p?<?0.001). Allergic asthma patients incurred 39% greater per-patient-per-year all-cause costs (allergic: $4008; non-allergic: $2889, p?<?0.001) and 79% greater asthma-related costs (allergic: $1063; non-allergic: $592, p?<?0.001) than non-allergic asthma patients. Conclusions: These results indicate, even in a relatively healthy population, allergic asthma is associated with greater HCRU and costs. Guideline-recommended IgE allergy tests should be employed in distinguishing the two forms of asthma, to optimize patient management and reduce costs.     

Circulating adhesion molecules and arterial stiffness

Damage to or stimulation of the endothelium leads to the increased expression and release of molecules that trigger leukocyte homing, adhesion and migration into the subendothelial space, which are fundamental stages of the development and progression of atherosclerosis.1 Among these, adhesion molecules play a key role. Adhesion molecules are substances that mediate the interaction between cells, their extracellular matrices and endothelial surfaces. They function as receptors that trigger intracellular pathways and participate in the control of vital processes.2Once expressed on the endothelial surface, soluble forms of adhesion molecules may be found in the circulation, released either via shedding or proteolytic cleavage, and are considered markers of increased expression of membrane-bound adhesion molecules.3-5 Vascular cell adhesion molecule 1 (VCAM-1) and intercellular adhesion molecule 1 (ICAM-1) are two important members of the immunoglobulin gene superfamily of adhesion molecules and their potential role as biomarkers of diagnosis, severity and prognosis of cardiovascular disease has been investigated in a number of clinical studies.6Decreased arterial compliance is one of the earliest signs of adverse structural and functional changes within the vessel wall.7 Increased arterial stiffness represents a physiological aspect of ageing, however, this process can be accelerated by cardiovascular risk factors, and has been shown to be an independent predictor of cardiovascular morbidity and all-cause mortality in various populations.8-10Although studies have also demonstrated that increased arterial stiffness is associated with inflammation, data on the association between aortic distensibility and soluble adhesion molecules are sparse.11 The purpose of the present study was to determine the relationship between circulating ICAM-1 and VCAM-1 levels as inflammatory markers, and aortic stiffness in patients referred for echocardiographic examination.     

Ultrastructure of bronchial biopsies from patients with allergic and non-allergic asthma

Epithelial damage is commonly found in airways of asthma patients. The aim of this study was to investigate epithelial damage in allergic and non-allergic asthma at the ultrastructural level. Bronchial biopsies obtained from patients with allergic asthma (n=11), non-allergic asthma (n=7), and healthy controls (n=5) were studied by transmission electron microscopy. Epithelial damage was found to be extensive in both asthma groups. Both in basal and in columnar cells, relative desmosome length was reduced by 30-40%. In columnar cells, half-desmosomes (i.e., desmosomes of which only one side was present) were frequently noticed. Eosinophils showing piece-meal degranulation were commonly observed in allergic asthma. Degranulating mast cells were more often observed in allergic asthma. Goblet cell hyperplasia was only found in allergic asthma. Lymphocytes were increased in both groups. In both groups, the lamina densa of the basal lamina was thicker than the control by about 40-50%. In allergic asthma the lamina densa was irregular with focal thickening. While there was always a tendency for changes (epithelial damage, desmosomes, degranulating mast cells, basal lamina) to be more extensive in allergic asthma compared to non-allergic asthma, there was no significant difference between the two groups in this respect. Reduced desmosomal contact may be an important factor in the epithelial shedding observed in patients with asthma.     

Circulating adhesion molecules in sera of asthmatic children

Infiltration of cells into the lung in asthma is regulated by several expressions of cell adhesion molecules (CAMs) on cells present in the airways, and may play a role in the pathogenesis of bronchial asthma. We sought to evaluate the role of serum concentrations of the soluble forms of intercellular adhesion molecule-1 (sICAM-1), vascular cell adhesion molecule-1 (sVCAM-1), and E-selectin (sE-selectin) in the control of disease activity in acute asthma. Circulating levels of sICAM-1, sVCAM-1, and sE-selectin in sera from 15 normal control subjects and from 20 allergic asthmatic children with acute exacerbations who had returned to stable condition were determined by using commercially available enzyme-linked immunosorbent assay kits. The mean concentration of serum sICAM-1 levels was significantly higher during an acute exacerbation of asthmatic children than in those with stable asthma (19.41 +/- 10.65 ng/mL vs. 13.46 +/- 5.44 ng/mL; P < 0.001) or in control subjects (9.83 +/- 2.02 ng/mL; P < 0.001). For sVCAM-1 and sE-selectin, the mean serum concentration of sVCAM-1 was slightly higher in children during an acute exacerbation asthma than when stable. However, the differences did not reach statistical significance. The mean serum concentrations of sVCAM-1 and sE-selectin in acute asthma or stable asthma were significantly higher than in control subjects. This study provides further evidence that serum concentrations of sICAM-1, sVCAM-1, and sE-selectin are increased in acute asthma. These findings further confirm that leukocyte endothelial adhesion plays a role in inflammatory airway disease.     

Circulating adhesion molecules and severity of coronary atherosclerosis

BACKGROUND: Circulating leukocytes are recruited at atherosclerotic sites through a family of adhesion molecules. Circulating forms of adhesion molecules in peripheral blood can be quantified now. OBJECTIVE: To evaluate the relationship between circulating adhesion molecules and severity of coronary atherosclerosis. METHODS: Subjects included 81 patients undergoing diagnostic coronary angiography, 12 of whom had normal coronary arteries (control group). The remaining 69 patients with demonstrable coronary atherosclerosis were divided into two groups by use of Gensini scores, namely mild atherosclerosis (n = 36, Gensini score 1-20) and severe atherosclerosis (n = 33, Gensini score > 20). Serum levels of circulating intercellular adhesion molecule-1 (ICAM-1), vascular cellular adhesion molecule-1 (VCAM-1), and E-selectin of groups measured before angiography were compared. RESULTS: Circulating levels of ICAM-1 in members of mild and severe atherosclerosis groups were significantly higher than those in members of the control group, whereas there was no significant difference among circulating levels of VCAM-1 in members of the three groups. Circulating levels of E-selectin in members of the mild atherosclerosis group were significantly higher than those in members of the severe atherosclerosis and control groups. CONCLUSIONS: These findings suggest that E-selectin is related to the early stage, and ICAM-1 is related to the advanced stage, of coronary atherosclerosis. With progression of atherosclerosis, one-step adhesion by ICAM-1 could become more important than multistep adhesion involving E-selectin, ICAM-1, and VCAM-1. These molecules may serve as markers for severity of coronary atherosclerosis.     

Circulating leucocyte adhesion molecules in chronic venous insufficiency.

BACKGROUND: Enzyme-linked immunosorbent assay (ELISA) techniques have detected the existence of circulating forms of intercellular adhesion molecule-1 (ICAM-1), vascular endothelial adhesion molecule-1 (VCAM-1) and E-selectin, all of which mediate leucocyte-endothelial adhesion. This study determined whether circulating cell adhesion molecules were increased in patients with chronic venous insufficiency (CVI) which causes venous stasis. PATIENTS AND METHODS: Before and after walking and upon recovery blood samples were drawn from the saphenous vein in 20 CVI patients: 10 with varicose veins (group 1), 10 with deep venous insufficiency (group 2). 10 healthy controls were enrolled. The total leucocyte count and the soluble levels of ICAM-1, VCAM-1 and E-selectin were determined. RESULTS: After walking, the total leucocyte count decreased significantly (p < 0.01) only in group 2 and sICAM-1 and sVCAM-1 increased significantly (p < 0.01). Upon recovery, these significant differences remained in group 2. No significant modification was observed at any stage of the study in group 1 or in the control group. CONCLUSIONS: These results suggest persistently high levels of circulating adhesion molecules may contribute to worsen microvascular perfusion, which leads to the onset of trophic damage in CVI.     

Circulating adhesion molecules in patients with vibration-induced white finger

We investigated whether a relationship existed between soluble adhesion molecules and vascular damage from vibration-induced white finger. Thirty-five men exposed to vibration and 40 healthy control subjects were examined. Concentrations of soluble E-selectin intercellular adhesion molecules, and vascular cell adhesion molecules in serum were measured with sandwich enzyme-linked adhesion immunosorbent assay. Neither E-selectin nor intercellular adhesion molecule levels are elevated in men exposed to vibration with white finger compared to levels in men exposed to vibration without white finger and control subjects. The serum level of soluble vascular cell adhesion molecules is significantly increased in patients with vibration-induced white finger.     

Circulating adhesion molecules levels in type 2 diabetes mellitus and hypertension

BACKGROUND: Risk factors for atherosclerosis such as hypertension, type 2 diabetes, obesity and dyslipidemia affect endothelial function and stimulate adhesion molecules expression. The aim of the study was to examine endothelial activation in type 2 diabetes and hypertension as indicated by adhesion molecule levels and further to investigate whether the coexistence of the above conditions has a different effect. METHODS: Serum levels of soluble E-selectin, ICAM-1 and VCAM-1 were measured in 17 hypertensive type 2 diabetic patients (DM-HY), 32 normotensive type 2 diabetic patients (DM), 11 hypertensive nondiabetic patients (HY) and 15 healthy subjects. RESULTS: In diabetic patients (either DM-HY or DM), soluble E-selectin levels were significantly increased compared to healthy subjects (p<0.001). In HY patients, both sE-selectin (66.44+/-71.59 vs. 29.42+/-15.56 ng/ml, p=0.033) and sVCAM-1 (1529+/-433.33 vs. 1027+/-243.56 ng/ml, p=0.03) levels were found significantly higher compared to healthy subjects (p<0.05). The coexistence of diabetes and hypertension (DM-HY) did not have an additive effect on circulating adhesion molecules levels compared with the levels observed in either diabetes or hypertension. Systolic and diastolic blood pressure (BP) were independent factors correlated respectively with sE-selectin and sVCAM-1 levels (R=0.454, p=0.034 and R=0.578, p=0.005) in nondiabetic subjects (hypertensive and normotensive). CONCLUSIONS: Type 2 diabetes mellitus and hypertension induce endothelial activation as indicated by elevated levels of soluble adhesion molecules. This effect is not different when comorbidity is present.     

Circulating adhesion molecules in patients with chronic obstructive pulmonary disease

The place of adhesion molecules that have a role in the immigration of intravascular leukocytes to the tissue with inflammation in the pathogenesis of chronic obstructive pulmonary disease (COPD) is controversial. Our purpose in this study was to examine the levels of soluble intracellular adhesion molecule-1 (sICAM-1) and Mac-1 (CD11b/CD18), lymphocyte function associated antigen-1 (LFA-1) in both neutrophils and lymphocytes in stable patients with COPD and in the healthy control groups consisting of non-smokers, and in smokers without COPD and also to evaluate the relationship between the parameters related to the severity of the disease. Peripheral venous blood samples of all the individuals were collected, and levels of sICAM-1 was measured quantitatively with ELISA method. Flow cytometry was used for Mac-1 and LFA-1 levels. Twenty-four stable patients with COPD (group I), 13 smokers (group II) and 14 healthy non-smokers (group III) were included in this study. In the COPD group, 12 smokers patients were considered as group IA, and 12 patients with non-smokers and biomass exposure were considered as group IB. No statistically significant differences were seen in LFA-1 examined in peripheric blood (PB) neutrophils and lymphocytes and sICAM in groups I, II, and III. Mac-1 examined in PB neutrophils was found to be significantly lower in group I when compared to groups II and III, however no difference could be seen in smokers' group of II and the control group III. Mac-1 examined in PB lymphocytes were found to be higher in group I according to group II, however no statistically significant difference was seen between group I and control group. No statistically significant differences were seen in all adhesion molecules levels in group IA and group IB. As a result; it was found that Mac-1 levels in PB neutrophils were decreased with the developing of COPD and Mac-1 levels in PB lymphocytes were decreased in smokers, however increased following the development of COPD. No differences existed in sICAM and LFA-1 levels dependent on smoking and/or COPD.     

北京地区过敏性鼻炎及非过敏性鼻炎发病情况调查报告

目的了解北京地区过敏性鼻炎(AR)、非过敏性鼻炎(NAR)发病情况,掌握其流行病学特点。方法选择北京地区城区人口稳定社区整群抽样,专业人员入户问卷调查,统计鼻炎患病情况并进行分析。结果共发送问卷2 000份,收回有效问卷1 988份,其中初筛鼻炎患者194例(9.7%)。20.5%的患者合并眼部症状,19.1%的患者合并存在咳嗽、喘息等呼吸道症状。12.9%存在皮肤过敏。对其中102例通过皮肤点刺试验行过敏原筛查,58例(56.9%)过敏原检查阳性且与过敏原接触史相符,诊断为AR;44例(43.1%)过敏原筛查阴性,诊断为NAR。AR与NAR患者在年龄、性别方面差异没有统计学意义。15.9%NAR主诉症状发作存在明确季节性,84.1%NAR表现为常年发病,81.0%AR表现为常年发病,其中包括34.5%常年发作伴季节性加重,19.0%AR表现为明确的花粉过敏,并与花粉过敏原检查结果吻合。结论 AR与NAR临床表现相似,两者均80%以上表现为常年发病。AR的主要过敏原为尘螨。     

Circulating adhesion molecules in patients with stable coronary artery disease

To evaluate platelet and endothelial function in patients with stable coronary artery disease (CAD), we investigated levels of the plasma-soluble (s) adhesion molecules E-selectin (sE-selectin), P-selectin (sP-selectin), and intercellular adhesion molecule-1 (sICAM-1) in 74 patients (mean age, 53 +/- 8 years) with angiographically documented coronary artery disease. Levels were compared to 27 matched healthy control subjects. Patients were excluded if they had recent cardiovascular events or any illness that might influence platelet and endothelial cell function. Concentrations of sP-selectin were significantly higher in patients with stable CAD (276 +/- 61 ng/mL) compared with control subjects (188 +/- 32 ng/mL) (P = .0001), whereas sE-selectin and sICAM-1 levels were similar between the 2 groups. Pooling both groups showed that sICAM-1 correlated weakly with triglycerides (r = 0.240, P = .01) and sP-selectin correlated weakly with low-density lipoprotein cholesterol (r = 0.204, P = .04). Although plasma sICAM-1 concentrations were significantly increased in hypercholesterolemic patients compared with those of normocholesterolemic patients (P = .04), sP-selectin and sE-selectin levels were similar between the 2 groups. In conclusion, significantly increased sP-selectin levels, indicating platelet activation, were found in patients with stable CAD. No other sign of endothelial cell activation in these patients could be detected. Moreover, sP-selectin levels seem to reflect the activation of platelets rather than of endothelial cells.     

Novel clinical and serological aspects in non-allergic asthma

BACKGROUND: We have recently observed that skin reactivity to autologous serum injection is common in patients with non-allergic asthma. However, clinical significance of skin reactivity to autologous serum remains to be defined. OBJECTIVE: To evaluate the possible relation between skin reactivity to autologous serum and clinical and laboratory characteristics in a series of patients with non-allergic asthma. METHODS: Fifty-five patients with non-allergic asthma underwent in vivo autologous serum skin test (ASST) and in vitro basophil histamine release assay using basophils from a normal donor. Clinical and laboratory characteristics including peripheral blood eosinophilia, antinuclear antibodies and total IgE concentration were evaluated. As control, ASST was performed in 10 allergic asthmatic patients, 10 patients with allergic rhinitis and 10 normal subjects. RESULTS: ASST was positive in 29/55 non-allergic asthmatics (53%), whereas it was negative in all 30 control subjects (P<0.001). The sera of 6 out of 51 patients induced in vitro histamine release from autologous basophils. The sera from two patients induced histamine release from membrane IgE-stripped basophils. A significant predominance of female sex (83%) and a high incidence of antinuclear antibodies (ANA) positivity (55%) were found among ASST-positive patients. CONCLUSION: These findings indicate that ASST is positive in about half patients with non-allergic asthma and that a proportion of patients (16%) has functional evidence of circulating histamine-releasing factors. In addition, predominance of female sex and frequent ANA positivity are in line with an autoimmune basis of non-allergic asthma.     

Circulating endothelial cell/leucocyte adhesion molecules in ischaemic heart disease

Increased levels of the endothelial markers soluble E-selectin ( P  = 0.011), soluble thrombomodulin ( P  = 0.0001) and von Willebrand factor (VWF, P  < 0.0001) were found in 116 patients with ischaemic heart disease compared to an equal number of age- and sex-matched asymptomatic controls. In a multivariate analysis of the markers versus the major risk factors for atherosclerosis, VWF correlated with total cholesterol ( P  = 0.002) and E-selectin with sex (lower in women, P  = 0.004) and triglycerides ( P  = 0.007). The data point to profound differences in the release mechanisms of these three endothelial cell products and suggests that further studies into the roles of these molecules in coronary artery disease are warranted.     

Upper airway and skin symptoms in allergic and non-allergic asthma: Results from the Swedish GA2LEN study

Background: Allergic and non-allergic asthma are viewed as separate entities, despite sharing similarities. The aims of this study were to determine differences in symptoms from the upper airways and the skin in allergic and non-allergic asthma. The secondary aims were to identify childhood risk factors and to compare quality of life in the two asthma groups. Methods: This cohort (age 17–76 years) consisted of 575 subjects with allergic or non-allergic asthma and 219 controls. The participants participated in an interview, spirometry, FeNO, skin prick test, and responded to the Mini Asthma Quality of Life Questionnaire. Results: Self-reported allergic rhinitis was significantly more common in both allergic and non-allergic asthma (82.3 and 40.7%) groups compared with the controls. The prevalence of chronic rhinosinusitis (CRS) was similar in both asthma groups. Eczema was significantly more common in both asthmatic groups (72.3 and 59.8%) than controls (47.0%) (p < 0.001 and p = 0.012). Severe respiratory infection in childhood and parental allergy were risk factors for both allergic and non-allergic asthma groups. Quality of life was significantly lower in non-allergic than allergic asthma groups (p = 0.01). Conclusion: Concomitant symptoms from the upper airways and the skin were significantly more common in both allergic and non-allergic asthma. This indicates that non-allergic asthma has a systemic component with similarities to what is found in allergic asthma. There were similarities in the childhood risk factor pattern between the two types of asthma but asthma-related quality of life was lower in the non-allergic asthma group.     

Analysis of apoptotic cells in allergic and non-allergic nasal mucosa

BackgroundAlthough the mechanisms controlling the resolution of inflammatory processes are still not clear, it is thought that a number of inflammatory cells, including neutrophils and eosinophils, and ingestion of these cells by macrophages may be involved in the apoptotic cell process in allergic or non-allergic nasal tissues. We postulated that apoptosis of inflammatory cells may occur in vivo in nasal mucosa, thus regulating allergic and non-allergic inflammation, and to test this hypothesis we examined apoptotic cells in the nasal tissue of surgical specimens.MethodsHuman turbinates were obtained after conchotomy performed on patients with nasal obstruction refractory to medication. Nasal tissues were fixed in formalin and embedded in paraffin. The paraffin-embedded tissues were stained for apoptotic cells by terminal deoxynucleotidyl transferase-mediated deoxyuridine 5′-triphosphate (dUTP) nick end-labeling (TUNEL). To identify cell types undergoing apoptosis, double staining was performed by combining TUNEL and immunohistochemistry.ResultsThe majority of TUNEL-positive cells were identified as leukocytes. Most TUNEL-positive cells found in these tissues represented granulocytes. A higher proportion of TUNEL-positive cells was found to be macrophages and most TUNEL-positive macrophages had intact nuclei and contained phagocytosed TUNEL-positive material (assumed to be apoptotic cells or bodies) in the cytoplasm.ConclusionsThese experiments represent the demonstration of cell type-specific apoptosis in human nasal mucosa. The results may have an important clinical implication and also promote further investigation to control the apoptosis of these cells in health and disease.