Pneumococcal-specific IgG levels after 13-valent pneumococcal conjugate vaccination in Nigerian children with sickle cell disease.

BACKGROUND: Children with sickle cell disease (SCD) are particularly susceptible to pneumococcal infection. Administration of the 13-valent conjugate pneumococcal vaccine which is now available in Nigeria may help to reduce the incidence. OBJECTIVES: To determine the serum level of pneumococcal-specific IgG (PIgG) in a cohort of patients with SCD after administration of a single-dose of a 13-valent pneumococcal conjugate vaccine. METHODS: The study was conducted between December 2011 and March 2012 among children with SCD aged 5 months to 5 years attending the sickle cell clinic in five public hospitals in Lagos. Altogether, 151 children with SCD and 52 without it (controls) were recruited by convenience sampling from the sickle cell clinics and well-child clinics. Blood samples were collected for PIgG concentrations before and 2 months after a single dose of the Prevenar 13 vaccine. Seroconversion was defined as a fourfold or greater increase in antibody concentration after vaccination while those with PIgG concentrations ≥200 µU/ml were considered to have protective levels. RESULTS: The age range of the total study group was 5-60 months with a mean (SD) of 39.04 (15.44) months and a median of 39 months. The mean (SD) ages of subjects with and without SCD were 38.91 (15.75) months and 16.39 (15.45) months, respectively. The PIgG concentration 2 months post-vaccination was significantly greater than the pre-vaccination levels in all age categories in both groups and almost all subjects had protective PIgG concentrations 2 months after vaccination. A four-fold increase in PIgG concentration was detected more commonly in the controls than in SCD patients. CONCLUSION: Prevenar 13 provided protective immunity in all vaccinated children but those under 2 years of age who had non-protective levels pre-vaccination benefited the most.

Allergy sensitization and asthma among 13-14 year old school children in Nigeria.

BACKGROUND: The prevalence of asthma and role of atopy in asthma among children has not been clearly defined in Nigeria. OBJECTIVE: To determine the prevalence of asthma and investigate risk factors related to allergy sensitization among urban and rural school children in southwest Nigeria. METHODS: Validated ISAAC questionnaire was administered to 1736 high school children in randomly selected schools in rural and urban communities. Identified asthma cases were matched to controls. Allergy skin tests, blood eosinophil count, serum IgE and stool examination for parasites were performed. Dust samples from homes were also collected and analyzed for allergens. RESULTS: The prevalence of asthma was 7.5% (95% CI 6.0 to 9.2%) and 8% (95% CI 6.0-10.4%) in the rural and urban communities respectively . Risk factors for asthma included cigarette-smoking, cats in the home and family size. Eosinophil count (109/L) was elevated in asthmatics [0.70 (95% CI 0.48-1.11) vs. 0.32 (95% CI 0.19-0.69); p<0.01], but IgE levels were similar between the two groups (298±229 IU/mL vs. 288±257; p=0.97). Positive skin tests to cat hair, cockroach, mango blossom and mouse epithelium were more frequent in asthmatics than in healthy controls, especially in the rural communities. There was no correlation between allergens in dust collected from homes and skin test reactivity. CONCLUSION: Asthma prevalence is similar in rural and urban children in Southwest Nigeria and atopy with elevated IgE was not observed to be a major factor for asthma in our cohort of children in both communities.

Atopy is associated with asthma in adults living in rural and urban southwestern Nigeria.

RATIONALE: Factors affecting the course of asthma are not clearly understood in rural and urban communities within low-resource countries. Furthermore, the interactions between atopy, environmental exposure, and helminthic infections in modulating asthma have not been well investigated. OBJECTIVES: To conduct a feasibility study to examine the relationship between atopy and asthma in adults at two rural Health Centers and urban university college hospital in southwestern Nigeria. METHODS: A convenient sample of 55 consecutive patients with stable physician-diagnosed asthma and 55 age-matched nonasthmatic controls seen at the outpatient clinics in two rural Health Centers and an urban university hospital were enrolled. All subjects underwent blood test, allergy skin test, and stool examination for ova and parasites. Wilcoxon sign-rank tests were used to compare serum eosinophilia and allergy skin test between the two groups. RESULTS: Asthmatics in both urban and rural settings had significantly more positive skin reactions to house dust mite, cockroach, mold, and mouse epithelium than nonasthmatic controls (p < .05). Mean total serum IgE was also significantly higher in asthmatics than in nonasthmatic controls (360 vs. 90 IU/L, p <.001). Stool parasitemia was infrequent in both groups and not statistically significant. CONCLUSION: Atopy is associated with adult asthma in southwest Nigeria. Larger studies to confirm the nature of this association and to examine the role of helminthic infection and other environmental factors on the expression of asthma are needed.

Laryngospasm and paradoxical bronchoconstriction after repeated doses of beta 2-agonists containing edetate disodium.

A 22-year-old woman with mild intermittent asthma, who had no previous history of an adverse reaction to an albuterol metered-dose inhaler, developed paradoxical bronchoconstriction after inhalation of the fourth dose of an albuterol nebulizer solution. She experienced the same symptoms and laryngospasm with repeated inhalations of albuterol and metaproterenol nebulizer solutions that contained edetate disodium. Each episode responded to racemic and subcutaneously administered epinephrine. To our knowledge, this is the first report of paradoxical bronchoconstriction and laryngospasm due to repeated doses of beta 2-agonist solutions with edetate disodium.

Prolongation of the QT interval related to cisapride-diltiazem interaction.

Cisapride, a cytochrome P450 3A4 (CYP3A4) substrate, is widely prescribed for the treatment of gastrointestinal motility disorders. Prolongation of QT interval, torsades de pointes, and sudden cardiac death have been reported after concomitant administration with erythromycin or azole antifungal agents, but not with other CYP3A4 inhibitors. A possible drug interaction occurred in a 45-year-old woman who was taking cisapride for gastroesophageal reflux disorder and diltiazem, an agent that has inhibitory effect on CYP3A4, for hypertension. The patient was in near syncope and had QT-interval prolongation. After discontinuing cisapride, the QT interval returned to normal and symptoms did not recur. We suggest that caution be taken when cisapride is prescribed with any potent inhibitor of CYP3A4, including diltiazem.

Giant cell arteritis manifesting as chronic cough and fever of unknown origin.

A 57-year-old white man sought medical attention because of chronic cough and fever of unknown origin. An extensive work-up over 4 weeks, including repeated blood cultures, chest roentgenograms, a gallium scan, and computed tomographic scans of the sinuses, chest, and abdomen, was nondiagnostic. The patient was referred to our institution for bronchoscopy. Further analysis of his history revealed that he had a headache in conjunction with the cough and an episode of a flashing color design in his left eye 1 week before assessment. The erythrocyte sedimentation rate was 115 mm in 1 hour. A biopsy of the temporal artery showed granulomatous inflammation of the vessel wall with multinucleated giant cells, histiocytes, lymphocytes, plasma cells, and few eosinophils. The multinucleated giant cells were closely related to the fragmented elastic lamina. Corticosteroid therapy resulted in prompt resolution of the chronic cough and fever. Giant cell arteritis should be considered in the differential diagnosis of chronic cough.

Angiotensin-converting enzyme and neutral endopeptidase modulate smokeless tobacco-induced increase in macromolecular efflux from the oral mucosa in vivo.

Smokeless tobacco elicits plasma exudation from the oral mucosa that is mediated by bradykinin, and it decreases the activity of tissue angiotensin-converting enzyme (ACE), a peptidase that cleaves and inactivates bradykinin. However, the mechanisms regulating bradykinin-induced responses during exposure to smokeless tobacco are uncertain. The purpose of this study was to begin to address this issue by determining whether inhibitors of ACE and neutral endopeptidase (NEP), a membrane-bound peptidase widely distributed in the oral mucosa that also cleaves and inactivates bradykinin, potentiate a smokeless tobacco-induced increase in macromolecular efflux from the oral mucosa in vivo. Using intravital microscopy, we found that suffusion of an aqueous extract of smokeless tobacco elicited a significant concentration-dependent increase in fluorescein isothiocyanate-labeled dextran (molecular mass 70 kd) leaky site formation in the hamster cheek pouch (p < 0.05). This response was significantly potentiated by captopril and lisinopril, two ACE inhibitors, and by phosphoramidon and thiorphan, two NEP inhibitors (p < 0.05). The effects of ACE and NEP inhibitors were additive. By contrast, a mixture of proteinase inhibitors consisting of leupeptin, Bestatin, and DL-2-mercaptomethyl-3-guanidinoethylthiopropanoic acid had no significant effects on smokeless tobacco extract-induced responses. Overall, these data suggest that ACE and NEP each play a role in modulating a smokeless tobacco-induced increase in macromolecular efflux from the in situ oral mucosa, in part by regulating local bradykinin catabolism.

Purified ACE attenuates smokeless tobacco-induced increase in macromolecular efflux from the oral mucosa.

The purpose of this study was to determine whether purified angiotensin I-converting enzyme (ACE) attenuates smokeless tobacco extract (STE)-induced increase in macromolecular efflux from the in situ oral mucosa. By using intravital microscopy, we found that suffusion of an aqueous extract of smokeless tobacco elicited significant concentration-dependent leaky site formation and increase in clearance of fluorescein isothiocyanate-labeled dextran (mol mass, 70 kDa) from the hamster cheek pouch (P < 0.05). Suffusion of purified rabbit lung ACE significantly attenuated these responses in a concentration-dependent fashion (P < 0.05). These effects were specific because purified ACE also significantly attenuated the increase in macromolecular efflux elicited by bradykinin, which is produced in the cheek pouch during suffusion of STE, but did not attenuate the increase elicited by adenosine. Moreover, suffusion of heat-inactivated purified ACE and purified superoxide dismutase had no significant effects on STE- and bradykinin-induced responses. Collectively, these data suggest that exogenous ACE attenuates STE-induced increase in macromolecular efflux from the in situ oral mucosa, in part, by promoting local bradykinin catabolism.

Decrease in immunoreactive neutral endopeptidase in uvula epithelium of patients with obstructive sleep apnea.

The purpose of this study was to determine whether neutral endopeptidase (NEP; EC3.4.24.11) is decreased in the uvula epithelium of patients with obstructive sleep apnea (OSA). Tissues were obtained by uvulopharyngopalatoplasty in seven patients with moderate OSA and by autopsy in five individuals not known to have OSA. Using antisera to human NEP and immunoperoxidase staining, we found that NEP was localized in uvula epithelial cells of both patients with OSA and controls. However, there was a significant decrease in the number of epithelial cells staining for NEP in patients with OSA relative to controls (67 +/- 10 cells versus 261 +/- 33 cells, in 5 randomly selected high-power microscopic fields, respectively; mean +/- SEM; p < .05). The intensity of staining for NEP was similar in both groups. We conclude that immunoreactive NEP is significantly decreased in the uvula epithelium of patients with OSA.

Exhaled pentane and nitric oxide levels in patients with obstructive sleep apnea.

BACKGROUND: Upper airway inflammation is present in patients with obstructive sleep apnea (OSA). OBJECTIVE: To determine whether exhaled pentane and nitric oxide (NO) levels, two nonspecific markers of inflammation, are increased in patients with OSA. METHODS: Exhaled nasal and oral pentane and NO levels were determined before and after sleep in 20 patients with OSA (apnea-hypopnea index, 48+/-7; mean+/-SEM) and eight healthy control subjects. RESULTS: In patients with OSA, exhaled nasal and oral pentane levels after sleep were significantly higher than presleep values (6.1+/-1.2 nM vs 3.4+/-0.4 nM, and 7.0+/-1.3 nM vs 4.2+/-0.4 nM, respectively; p<0.05). Likewise, exhaled nasal and oral NO levels after sleep were significantly higher than presleep values in patients with OSA (39.7+/-3.8 ppb vs 28.4+/-2.9 ppb and 10.9+/-1.5 ppb vs 6.6+/-0.8 ppb, respectively; p<0.05). By contrast, there were no significant differences in exhaled nasal and oral pentane, and nasal NO levels before and after sleep in control subjects. Exhaled oral NO levels were significantly increased after sleep in comparison to presleep values in control subjects (p<0.05). CONCLUSION: Exhaled nasal pentane and NO levels are increased after sleep in patients with moderate-severe OSA. These data suggest that upper airway inflammation is present in these patients after sleep.

Exhaled pentane levels in acute asthma.

BACKGROUND: Exhaled pentane, a product of lipid peroxidation, has been proposed as an objective, nonspecific, and noninvasive marker of active inflammation. Reactive oxygen species, which elicit lipid peroxidation, are increased in asthma and contribute to airway dysfunction. OBJECTIVE: To determine whether exhaled pentane levels are increased in acute asthma, and whether they decrease once acute asthma subsides. METHODS: Expired air was collected through a mouthpiece into a pentane-impermeable collection bag from 12 patients (40+/-5 years; mean+/-SEM) presenting to the emergency department of the University of Illinois Hospital in Chicago with acute asthma. Exhaled air was also collected after discharge from the hospital once acute asthma subsided. Eleven patients with stable asthma (40+/-5 years) and 17 healthy volunteers (31+/-5 years) served as control subjects. Exhaled air and ambient room air were analyzed for pentane content by gas chromatography. Peak expiratory flow rates were determined in each subject. RESULTS: Peak expiratory flow rates were 202+/-29 L/min during acute asthma and 327+/-26 L/min once acute asthma subsided (p<0.05). Exhaled pentane levels were 8.4+/-2.9 nmol/L during acute asthma and decreased significantly to 3.5+/-0.5 nmol/L once acute asthma subsided (p<0.05). Exhaled pentane levels were similar in patients with stable asthma and normal control subjects (3.6+/-0.4 nmol/L and 2.6+/-0.2 nmol/L, respectively; p>0.05). No pentane was detected in ambient air. CONCLUSION: Exhaled pentane levels are increased in patients with acute asthma and decrease significantly once acute asthma subsides.

Characteristics of predominantly nonwhite patients with frequent hospitalizations for acute asthma in Chicago.

The purpose of this study was to determine the characteristics of predominantly nonwhite patients with recurrent visits to the emergency department (ED) and admissions to an inner-city hospital in Chicago for acute asthma. Over a 21-month period, two groups of age and gender-matched individuals with asthma seen at the University of Illinois at Chicago Medical Center were studied: group I included 26 patients with frequent visits to the ED and no more than one admission for acute asthma/year; and group II included 28 patients with recurrent visits to the ED and two or more admissions for acute asthma/year. We found that 70% of all patients (38/54) were females and 72% (39/54) were African-Americans. The latter predominated in group II (25/28; 89%). There were no significant differences in public aid recipients, baseline FEV1, type of antiasthma medications used, and illicit drug use between the two groups. However, group II reported more asthma onset before the age of 11 years and used higher daily doses of inhaled corticosteroids than group I (p < 0.05). The average duration of hospital stay in group II was significantly longer (3.3 +/- 0.4 days vs. 2.4 +/- 0.3 days, respectively, mean +/- SEM, p < 0.05), and the average cost per hospitalization in group II significantly exceeded that of group I ($5122 +/- $590 vs. $3740 +/- $450, respectively, p < 0.05). We conclude that African-American females are seen more frequently in the ED for acute asthma and admitted to the hospital in Chicago. They develop asthma before the age of 11 years, use higher daily doses of inhaled corticosteroids, and contribute significantly to the high cost of asthma care.

Mechanisms of smokeless tobacco-induced oral mucosa inflammation: role of bradykinin.

The purpose of this study was to determine whether an aqueous extract of smokeless tobacco (moist snuff) increases clearance of macromolecules from postcapillary venules in the in situ oral mucosa and, if so, whether bradykinin mediated this response. Using intravital microscopy, we found that 20-min suffusion of the extract elicited significant concentration-dependent leaky site formation and increase in clearance of FITC-dextran (molecular mass, 70 kDa) from the hamster cheek pouch (p < 0.05). These responses were associated with a significant increase in bradykinin-like immunoreactivity in the suffusate. Smokeless tobacco extract-induced leaky site formation and increase in clearance of FITC-dextran were significantly attenuated by NPC 17647 and Hoe 140 (p < 0.05), two bradykinin B2 receptor antagonists, but not by desArg9,[Leu8]bradykinin, a bradykinin B1 receptor antagonist. Both bradykinin B2 receptor antagonists had no significant effects on adenosine-induced responses. Indomethacin had no significant effects on smokeless tobacco extract-induced responses. Exposure to smokeless tobacco extract was associated with a significant decrease in angiotensin I-converting enzyme activity and a small, but significant, increase in neutral endopeptidase 24.11 activity in the cheek pouch, two peptidases widely distributed in the microcirculation that cleave and inactivate bradykinin (p < 0.05). Overall, these data suggest that smokeless tobacco elicits plasma exudation in the oral mucosa in vivo in a specific fashion, and that this response is mediated by bradykinin.

Neutral endopeptidase modulates VIP-induced vasodilation in hamster cheek pouch vessels in situ.

The purpose of this study was to determine whether vasoactive intestinal peptide (VIP) dilates resistance arterioles in the in situ systemic circulation and whether inhibitors of neutral endopeptidase (NEP) and angiotensin I-converting enzyme (ACE), two membrane-bound metalloenzymes that are widely distributed in the microcirculation and cleave and inactive VIP, potentiate this response. Using intravital microscopy, we found that VIP (0.05 and 0.1 nmol) induced significant vasodilation in the hamster cheek pouch (13 +/- 1 and 20 +/- 2% increase from baseline, respectively; mean +/- SE; P < 0.05). These responses were significantly potentiated by topical application of phosphoramidon and thiorphan, two relatively selective NEP inhibitors, but not by captopril, a relatively selective ACE inhibitor. Furthermore, suffusion of a mixture of proteinase inhibitors consisting of leupeptin, Bestatin, and DL-2-mercaptomethyl-3-guanidinoethylthiopropanoic acid to inhibit serine proteinases, including mast cell tryptase, aminopeptidases, and carboxypeptidase N, respectively, had no significant effects on VIP-induced responses. These data indicate that VIP elicits vasodilation in the in situ systemic microcirculation and that NEP modulates this response.

Inflammation in the uvula mucosa of patients with obstructive sleep apnea.

This study was conducted to determine whether inflammation is present in the uvula mucosa of patients with obstructive sleep apnea (OSA). Uvulas were obtained by uvulopalatopharyngoplasty in 21 patients with moderate OSA (mean apnea/hypopnea index and standard error of the mean: 32 +/- 4) and by autopsy in 5 individuals not known to have OSA. Using point counting in five randomly selected high-power microscopic fields (X100), the authors found that the number of leukocytes in the lamina propria of the uvula mucosa was significantly higher in patients with OSA than in the controls (179 +/- 12 cells vs. 71 +/- 4 cells, respectively; P < .05). This was due to a significant increase in the number of plasma cells in patients with OSA as compared with controls (89 +/- 15 cells vs. 21 +/- 5 cells, respectively; P < .05). The thickness of the lamina propria (an index of interstitial edema) was also significantly increased in patients with OSA compared with controls (0.99 +/- 0.12 mm vs. 0.27 +/- 0.02 mm, respectively; P < 0.05). The authors conclude that inflammation, characterized by plasma cell infiltration and interstitial edema, is present in the uvula mucosa of patients with moderate OSA. They also suggest that soft palate inflammation contributes to upper airway occlusion observed during sleep in these patients.

Aqueous smokeless tobacco extract impairs endothelium-dependent vasodilation in the oral mucosa.

The purpose of this study was to determine whether an aqueous extract of smokeless tobacco (moist snuff) modulates vasomotor tone in the oral mucosa in situ and, if so, to determine the mechanisms that mediated these responses. Using intravital microscopy, we found that the extract had no significant effects on diameter of resistance (second-order) arterioles [44 +/- 5 (SD) microns] in the hamster cheek pouch. However, it significantly attenuated vasodilation elicited by two endothelium-dependent agonists, acetylcholine and bradykinin (P < 0.05). These effects were specific because smokeless tobacco extract had no significant effects on vasodilation elicited by nitroglycerin, an endothelium-independent agonist. Indomethacin, a cyclooxygenase inhibitor, and SQ-29548, a thromboxane A2/prostaglandin H2-receptor antagonist, abrogated the attenuating effects of smokeless tobacco extract on acetylcholine- and bradykinin-induced vasodilation. These data indicate that an aqueous extract of smokeless tobacco impairs endothelium-dependent vasodilation in the oral mucosa in situ in a specific fashion and that these effects are mediated, in part, by cyclooxygenase products of arachidonic acid metabolism that stimulate thromboxane A2/prostaglandin H2 receptors.

Stable VIP analogue Ro-24-9981 potentiates substance P-induced plasma exudation in hamster cheek pouch.

The purpose of this study was to determine whether vasoactive intestinal peptide (VIP; 300 nM) and a stable cyclic analogue of VIP, Ro-24-9981 (226 nM), modulated neurogenic plasma exudation in the oral cavity in situ and, if so, to determine the mechanisms that mediated these responses. With the use of intravital microscopy, we found that suffusion of substance P induced a significant concentration-dependent formation of fluorescein-isothiocyanate-dextran (mol wt 70 kDa) leaky sites in the hamster cheek pouch (P < 0.05). These effects were significantly and stereospecifically attenuated by NG-nitro-L-arginine methyl ester, an inhibitor of NO synthase, and restored by L-arginine, the substrate for NO synthase (P < 0.05). Topical application of human VIP and Ro-24-9981 had no significant effects of leaky site formation. In addition, human VIP had no significant effects on substance P-induced responses. By contrast, Ro-24-9981 significantly potentiated substance P- and capsaicin-induced leaky site formation (P < 0.05). The effects of Ro-24-9981 on substance P-induced responses were significantly attenuated by NG-nitro-L-arginine methyl ester and restored by L-arginine (P < 0.05). Indomethacin had no significant effects on Ro-24-9981-induced responses. Ro-24-9981 had no significant effects on adenosine- and calcium ionophore A-23187-induced leaky site formation. Collectively, these data suggest that VIP plays no significant role in modulating neurogenic plasma exudation in the oral mucosa. By contrast, Ro-24-9981 amplified this response in a specific receptor-mediated fashion.

Short-term exposure to lipopolysaccharide is associated with microvascular contractile dysfunction in vivo.

The purpose of this study was to determine whether short-term exposure of resistance arterioles to lipopolysaccharide in situ is associated with changes in vasomotor tone. Using intravital microscopy, we found that suffusion of Escherichia coli lipopolysaccharide (3 micrograms/ml) over hamster cheek pouch arterioles for 1 h was associated with a significant immediate biphasic response: vasoconstriction followed by vasodilation (p < 0.05). The former was attenuated by indomethacin, and the latter by SK&F 108566, a selective, non-peptide angiotension II receptor antagonist (p < 0.05). The nitric oxide synthase inhibitor, NG-L-nitro arginine, had no significant effects on lipopolysaccharide-induced responses. Allopurinol, a scavenger of reactive oxygen species, significantly attenuated lipopolysaccharide-induced vasodilation. Acetylcholine- and nitroglycerin-induced vasodilation were significantly potentiated after lipopolysaccharide. These responses were recorded in the absence of any significant changes in systemic arterial blood pressure. Collectively, these data suggest that short-term exposure of the peripheral microcirculation to lipopolysaccharide in situ is associated with an ischemia-reperfusion-like injury. These changes may contribute to end organ failure observed several hours after exposure to lipopolysaccharide.

Chronic eosinophilic pneumonia and idiopathic bronchiolitis obliterans organizing pneumonia: comparison of eosinophil number and degranulation by immunofluorescence staining for eosinophil-derived major basic protein.

OBJECTIVE: To undertake additional assessment of the possible overlap between bronchiolitis obliterans organizing pneumonia (BOOP) and chronic eosinophilic pneumonia (CEP). DESIGN: We retrospectively reviewed open-lung biopsy specimens from six patients with CEP, five patients with idiopathic BOOP, and four patients with secondary BOOP, encountered during the 5-year period 1986 through 1991, for the presence of eosinophils and extent of eosinophil degranulation. MATERIAL AND METHODS: Using previously described immunofluorescence methods for detection of intact eosinophils and extracellular deposition of eosinophil-derived major basic protein, we counted the number of eosinophils per x160 microscopic field and evaluated the extent of eosinophil degranulation semiquantitatively. RESULTS: The median numbers of eosinophils were 221 (range, 26 to 343) in cases of CEP, 7 (range, 1 to 65) in cases of idiopathic BOOP, and 7.5 (range, 1 to 39) in cases of secondary BOOP. More eosinophils were found in CEP than in idiopathic BOOP or all cases of idiopathic and secondary BOOP. We found no differences in the extent of eosinophil degranulation among the three groups, although a tendency for more degranulation was noted in cases of CEP. CONCLUSION: Even though clinical and histologic overlap may exist between CEP and idiopathic BOOP, the exact relationship and the role of the eosinophil in idiopathic BOOP remain to be determined.