Search

Silent brain infarction (SBI) and increased levels of soluble CD40 ligand (sCD40L) and soluble P-selectin (sP-selectin) are associated with an increased risk of cerebrovascular disease.The aim of this study was to evaluate whether SBI and serum levels of sCD40L and sP-selectin are increased in patients with obstructive sleep apnea (OSA).SBI was studied by brain magnetic resonance images in 50 male patients with OSA and 15 obese male control subjects who were free of comorbidities. In addition, the effects of 3 months of treatment with nasal continuous positive airway pressure (nCPAP) on serum parameters were studied in 24 patients with moderate to severe OSA.The percentage of SBI in patients with moderate to severe OSA (25.0%) was higher than that of obese control subjects (6.7%) or patients with mild OSA (7.7%). Serum levels of sCD40L and sP-selectin were significantly higher in patients with moderate to severe OSA than in obese control subjects (p0.05) or patients with mild OSA (p0.05). In addition, nCPAP significantly decreased serum levels of sCD40L (p0.03) and sP-selectin (p0.01) in patients with moderate to severe OSA.These results suggest that serum levels of sCD40L and sP-selectin are elevated and SBI is more common in patients with moderate to severe OSA, leading to elevated cerebrovascular morbidity. Moreover, nCPAP may be useful for decreasing risk in patients with moderate to severe OSA.

Increased carotid intima-media thickness (IMT) and increased serum levels of inflammatory markers, such as C-reactive protein (CRP), interleukin (IL)-6, and IL-18, are associated with an increased risk of cardiovascular and cerebrovascular diseases. The aim of this study was to evaluate whether carotid IMT, a useful marker for early atherosclerosis, is associated with these inflammatory markers in patients with obstructive sleep apnea (OSA). Carotid IMT was investigated with ultrasonography in 36 patients with OSA and 16 obese control subjects. Serum levels of CRP, IL-6, and IL-18 were measured at 5:00 A.M. Carotid IMT (p < 0.001) and serum levels of CRP (p < 0.003), IL-6 (p < 0.005), and IL-18 (p < 0.03) of patients with OSA were significantly higher than those of obese control subjects. Carotid IMT was significantly correlated with serum levels of CRP (r = 0.61, p = 0.0001), IL-6 (r = 0.41, p = 0.01), and IL-18 (r = 0.45, p = 0.005), duration of OSA-related hypoxia (r = 0.60, p = 0.0001), and severity of OSA (r = 0.50, p = 0.002). In addition, the primary factor influencing carotid IMT was duration of hypoxia during total sleep time (p = 0.036). These results suggest that OSA-related hypoxia and systemic inflammation might be associated with the progression of atherosclerosis and thus might increase the risks of cardiovascular and cerebrovascular morbidity in patients with OSA.

Study objectives: Tumor necrosis factor (TNF)- is involved in the pathogenesis of atherosclerosis. In the present study, we examined TNF- production by monocytes, serum levels of TNF-, and the effects of nasal continuous positive airway pressure (nCPAP) in patients with obstructive sleep apnea syndrome (OSAS). Design: Prospective observational study. Setting: University hospital. Subjects: Twenty-four patients with OSAS, 15 obese control subjects, and 12 healthy subjects. Measurements and results: After polysomnography, venous blood was collected at 5 AM. Spontaneous production of TNF- by monocytes for 24 h and serum levels of TNF- were investigated. In addition, patients with moderate-to-severe OSAS were treated with nCPAP for 1 month, and spontaneous production of TNF- by monocytes and serum levels of TNF- were also measured. Spontaneous production of TNF- by monocytes was significantly higher in patients with moderate-to-severe OSAS than in patients with mild OSAS (p < 0.0001), obese control subjects (p < 0.0001), or healthy subjects (p < 0.0001). Serum levels of TNF- were also significantly higher in patients with moderate-to-severe OSAS than in patients with mild OSAS (p < 0.03), obese control subjects (p < 0.0005), or healthy subjects (p < 0.0001). Duration of hypoxia during total sleep time was independently associated with spontaneous production of TNF- by monocytes in patients with OSAS and healthy and obese control subjects. nCPAP significantly decreased spontaneous production of TNF- by monocytes (p < 0.03) and serum levels of TNF(p < 0.05) in patients with moderate-to-severe OSAS. Conclusions: Spontaneous production of TNF- by monocytes and serum levels of TNF- are elevated in patients with moderate-to-severe OSAS but are decreased by nCPAP. (CHEST 2004; 126:1473–1479)

Interleukin (IL)-12 production and IL-12 receptor (IL-12R) beta2 chain expression were investigated in patients with allergic asthma successfully treated with rush immunotherapy (RIT) and control patients with mild allergic asthma. Peripheral blood mononuclear cells (PBMCs) were stimulated with Dermatophagoides farinae (Der f), and production of cytokines was measured. Furthermore, the effects of cytokines on IL-12R beta2 chain expression on CD4(+) T cells were investigated. Production by PBMCs of IL-12 and IFN-gamma was significantly higher and production of IL-4 was significantly lower after stimulation with Der f allergen in RIT-treated patients than in control patients. Significant increases in the expression of IL-12R beta2 chain before and after stimulation of CD4(+) T cells with IL-12 or IFN-gamma were observed in RIT-treated patients compared with that in control patients. Allergen RIT increases IL-12 production and IL-12R beta2 chain expression and thus may convert cytokine production from Th2 to Th1 or Th0 type in allergic asthma.

Eosinophilic gastroenteritis (EGE) is characterized by eosinophilic infiltration of the digestive organs, most commonly of the stomach and the duodenum. Symptoms of EGE are nonspecific and include nausea, vomiting, abdominal pain, dyspepsia, malabsorption, ascites and weight loss. The various symptoms of EGE depend on its location and the depth of gastrointestinal eosinophil infiltration. We report a case presenting with acute pancreatitis caused by a milk allergy. The patient’s symptoms rapidly improved after treatment with corticosteroids, and he remained symptom-free for more than 20 months by the elimination of cow’s milk from his diet. Serum titers of pancreatic enzymes and total bilirubin simultaneously recovered and blood eosinophil counts normalized. The causative allergens of EGE are too various to detect; however, allergologic exams revealed that a cow’s milk allergy had provoked EGE in our case. Adult-onset cow’s milk allergies are rare; when seen, however, they may present severe complications such as anaphylaxis, gastroenteritis and pancreatitis. When unaccountable gastrointestinal symptoms are observed, EGE caused by food allergies should be included in the differential diagnosis.

A 30-year-old woman had refractory asthma. She had also experienced twice severe anaphylaxis episodes after ingesting peaches. The patient was extremely wary about reoccurrence of anaphylaxis and avoided ingesting any fruits, including peaches. She visited our hospital for testing and treatment for asthma and the peach allergy. Skin and serologic testing showed that she had a severe allergy to house dust, mites, and peaches. The food challenge test results showed that ingesting 6.5 g of the peach fruit induced dyspnea in the patient. Her asthma could not be controlled despite treatment involving a leukotriene receptor antagonist and combination inhalation of high-dose salmeterol xinafoate/fluticasone propionate. We advised the patient to keep strict avoidance ingesting peaches because of her food allergy. However, she hoped to overcome her food restrictions, especially those for fruits. We initiated treatment involving the recombinant humanized monoclonal anti-IgE antibody omalizumab (150 mg, once a month) to ensure that the asthma was controlled well and to improve the patient's diet. The asthmatic symptoms ameliorated, and the peak expiratory flow increased in a short time. We gradually reduced the restriction on peach consumption. This was achieved by rechallenging the patient with increasing doses of 290 mg of the peach fruit and was initiated at 28 weeks after starting omalizumab therapy. The restriction on peach consumption was lifted eventually, and the patient did not experience any allergic symptoms subsequently on ingesting peaches. Thus, for our patient, omalizumab therapy was highly effective in achieving remission from both asthma and peach allergy.

Matrix metalloproteinases (MMPs) are involved in the pathogenesis of cardiovascular diseases. We examined serum levels of MMP-9 and its inhibitor, tissue inhibitor of metalloproteinase-1 (TIMP-1), activity of MMP-9, and the effect of nasal continuous positive airway pressure (nCPAP) in patients with obstructive sleep apnea syndrome (OSAS). After polysomnography, venous blood was collected at 5:00 A.M. from 44 patients with OSAS and 18 control subjects who were obese, and serum levels of MMP-9, TIMP-1, and enzymatic activity of MMP-9 were measured. In addition, the effects of 1 month of treatment with nCPAP were studied in patients with moderate to severe OSAS. Although serum levels of MMP-9 (p < 0.03) and MMP-9 activity (p < 0.01) were higher in patients with OSAS than in control subjects who were obese, TIMP-1 levels did not differ significantly. In patients with OSAS, the severity of OSAS was the primary factor influencing levels (p < 0.01) and activity (p < 0.01) of MMP-9. nCPAP significantly decreased serum levels (p < 0.01) and activity (p < 0.001) of MMP-9 but did not affect TIMP-1 levels. Therefore, OSAS may increase risks of cardiovascular morbidity, and nCPAP might be useful for decreasing these risks.