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The prevalence of respiratory allergic diseases has been increasing in Southern Africa both in urban and in rural environments. Various factors may contribute toward this situation, namely, exposure to aeroallergens, such as grass pollens and house dust mites. However, other irritant environmental triggers, such as exposure to tobacco smoke and certain indoor and outdoor fumes, may also play a relevant part. Furthermore, certain parasitic and mycobacterial infections may act as allergic disease risk modifiers, although such an influence should be confirmed. Finally, certain cultural and socioeconomic factors may also influence accessibility to healthcare and adherence to treatment of these diseases. Keywords: asthma, rhinitis, prevalence, Southern Africa

Rhinosinusitis is a significant health problem, causing significant morbidity and resulting in considerable financial cost. Some patients suffer persistent or recurrent symptoms despite receiving optimal medical and surgical treatment. Rhinosinusitis can be acute or chronic, acute often due to viral or bacterial infections and chronic which is classified into chronic with nasal polyposids or chronic rhinosinusitis without nasal polyposis. The disease affects the quality of life significantly and presents a significant burden on health costs globally. The anatomical linkage of the nose with the paranasal sinuses facilitates a common pathology in both organs. Chronic rhinosinusitis (CRS) has heterogeneous origins, including viruses, bacteria, fungal infections, anatomical abnormalities, polyposis, and aspirin sensitivity. Other conditions such as human immunodeficiency virus acquired immunodeficiency and cystic fibrosis may also be predisposing factors. Nasal polyposis is often associated with increased numbers of Th2 lymphocytes, fibroblasts, goblet cells, mast cells, and eosinophils, with upregulation of IL-13 and the release of specific IgE to staphylococcal enterotoxins. There is recent evidence that antibiotic treatment may not be as effective as higher doses of intranasal steroids in acute uncomplicated rhinosinusitis, especially in those with allergic disease. The broad inflammatory basis of the pathology of CRS also reveals a cellular infiltrate theoretically suppressed by intranasal corticosteroids. This has been confirmed in recent clinical studies of CRS with or without polyps. A treatment approach based on such studies reported in the European Position Paper on Rhinosinusitis guidelines and a guideline summary are presented. The current review represents the proceedings of a session (3 talks) by the authors at the first Middle East-Asia Allergy, Asthma, Immunology Congress in 2009. Keywords: rhinosinusitis, nasal polyposis, corticosteroids

Complement component C6 is one of five terminal complement components incorporated into the membrane attack complex. Complete deficiency of C6 (C6Q0) leads to an increased susceptibility to Neisseria meningitidis infections, and affected individuals typically present with recurrent meningococcal disease. There is a relatively high prevalence of C6Q0 in the Western Cape, South Africa and three frameshift mutations have previously been described to be responsible for C6Q0 in this area—879delG, 1195delC, and 1936delG (current nomenclature). We have now genotyped a further nine genetically independent individuals with C6Q0, confirming previous reports that the most common defect in the Western Cape is 879delG. Moreover, we report the first identification of the 878delA mutation within the Western Cape, which has previously only been reported in individuals of African descent living in the United States or Europe. We also investigated the genotype of an Irish C6Q0 individual and her sibling, and report two previously undescribed mutations. One mutation alters a tyrosine codon to a stop codon within exon 10. The second mutation is within the 5′ donor splice site of intron 3, and would, in all probability, disrupt splicing. These two mutations were shown to segregate independently. We also discuss the nomenclature for reporting C6 and C7 gene mutations, as the current nomenclature does not follow the recognised guidelines.

Objective To obtain a current understanding of the mechanisms, clinical indications, efficacy, and safety of sublingual immunotherapy (SLIT) for the treatment of children and adults with allergic rhinitis, asthma, and allergic conjunctivitis. Methods A MEDLINE and Index Medicus search for peer-reviewed articles on SLIT was performed. Results Since the approval of SLIT by the World Health Organization in 1988, the efficacy and safety of SLIT have been confirmed in several new double-blind, placebo-controlled studies for monosensitized patients who are allergic to house dust mites, grass pollens, ragweed, and birch pollen. Documented immunologic responses to SLIT have included a decrease in serum eosinophilic cationic protein and interleukin 13 (IL-13) levels, an elevation in IL-12 levels, a reduction in late-phase responses, and increases in IgG4/IgE ratios. A Cochrane review of 22 studies confirmed the efficacy and safety of SLIT for patients with allergic rhinitis. A long-term asthma study showed sustained efficacy 5 years after discontinuing the vaccine. The safety of SLIT has been confirmed in postmarketing studies, and severe systemic adverse effects have never been reported. In view of its safety profile, SLIT is taken by the patient at home (away from specialized centers), and no specialized resuscitation facilities are required. Conclusion SLIT is a safe and effective therapeutic option for patients with allergic rhinitis and asthma. Because of its efficacy, safety, and ease of administration, it has been accepted in Europe, Southern Africa, Australasia, Southeast Asia, and the Middle East as a promising therapeutic option that can significantly alter the natural history of allergic disease without the risks of injection immunotherapy.

Objective To evaluate the effect of fexofenadine on driver behavior, decision-making, and reaction time in a blinded, randomized, parallel, placebo-controlled study. Methods A total of 259 male and female adult volunteers participated in a standardized BMW advanced driving test (the skid-pan test; Pretoria, South Africa) and a decision and reaction test of the Vienna Psychomotor Test System. The psychomotor test focused on mean decision times, mean reaction time, decision errors and reaction errors. After a baseline pretest run, the test was repeated 2.6 hours after ingesting either fexofenadine hydrochloride (180 mg) or placebo (the posttest; 1:1). Results Two hundred fifty-five volunteers were included in the final efficacy analysis (195 males and 60 females). There was a reduction in the road test time going from the pretest to the posttest, signifying a learning effect, and an increase in the decision time. Although there was a consistent increase in the number of errors committed in the road test, decision time, and reaction time, there were no significant differences between the placebo and the fexofenadine groups. Although significant differences were observed between men and women for the road test time ( P P P = 0.003), there were no differences between the fexofenadine and placebo groups in these subgroups. Conclusions No differences were found between the fexofenadine and placebo groups on reaction times, decision-making, driver behavior, or adverse effects.

The safety and efficacy of a 1% cream formulation of pimecrolimus, a selective, nonsteroid immunomodulator, was studied in infants with atopic dermatitis (AD).During a 6-week double-blind phase, 186 infants with mild/moderate AD were randomly assigned to twice-daily pimecrolimus cream 1% or vehicle. All patients were subsequently treated with open-label pimecrolimus for 20 weeks.At the end of the double-blind phase, 54.5% and 23.8% of patients in the pimecrolimus and vehicle groups, respectively, were clear or almost clear of AD (P.001). Similar improvements were observed in the Eczema Area and Severity Index, pruritus assessment, and the care giver's assessment. By the first return visit, 69.9% and 36.5% of pimecrolimus and vehicle-treated patients, respectively, achieved absent or mild pruritus. Efficacy during the double-blind phase was maintained throughout the open-label phase. Vehicle-treated patients transferring to open-label pimecrolimus rapidly achieved disease control comparable to those receiving continuous pimecrolimus. There were no significant differences between groups in application site reactions or skin infections. Most adverse events were mild or moderate and unrelated to treatment.Pimecrolimus was safe in infants with AD, with rapid and sustained efficacy. Pimecrolimus holds promise as a valuable new treatment option for the youngest patients with AD.

Background: The hypothesis that in atopic diseases the T-helper response is skewed toward a T H 2-type cytokine response was based on studies with mitogen stimulation, T-cell clones, or both. Objective: Using primary cultures, we investigated (1) whether atopic asthmatic patients have a T H 2 response and nonatopic subjects have a T H 1 response to allergen and (2) whether atopic patients have a decreased ability to mount T H 1 immune responses to mycobacterial antigens. Methods: The responses of PBMCs to allergen (house dust mite [HDM]) or purified protein derivative of Mycobacterium tuberculosis (PPD) stimulation from 10 severely and 14 moderately asthmatic patients (all allergic to HDM) were compared with those of 17 nonatopic healthy black (Xhosa) children. Results: HDM-stimulated proliferation, IL-5 release, and the IL-5/IFN-γ ratio were significantly increased in subjects with atopic asthma, whereas IFN-γ release was not significantly different. IL-4 levels were below the level of detection. PPD-stimulated proliferation, IL-5 release, IFN-γ release, and the IL-5/IFN-γ ratio were not significantly different among the groups. Each group had a significantly higher IL-5/IFN-γ ratio in response to HDM than to PPD (a T H 1 stimulus). Conclusion: Our study, which used primary cultures to investigate the hypothesis that nonatopic subjects have a T H 1 response to allergens, indicates that HDM stimulates a T H 2 cytokine response in both atopic and nonatopic subjects but that the response is enhanced in atopic patients. Our results with PPD suggest that normal and atopic asthmatic subjects can have a T H 1 cytokine response to mycobacteria, but there is a subgroup of atopic subjects that have a T H 2 response. (J Allergy Clin Immunol 2000;106:84-91.)

Background The For Angioedema Subcutaneous Treatment (FAST)-3 study was a phase III, randomized, double-blind, placebo-controlled study of icatibant (bradykinin B 2 receptor antagonist) in subjects with hereditary angioedema (HAE) resulting from C1-INH deficiency or dysfunction (type I/II). Objective To investigate icatibant efficacy and safety in subjects with acute HAE attacks. Methods Subjects with moderate to very severe cutaneous or abdominal symptoms received icatibant ( n = 43) or placebo ( n = 45). Five subjects with laryngeal (mild-to-moderate) first attacks received icatibant ( n = 3) or placebo ( n = 2), and 5 subjects with severe laryngeal first attacks received open-label icatibant. Results Cutaneous or abdominal attacks: icatibant significantly reduced median times (vs placebo) to 50% or more reduction in symptom severity (2.0 vs 19.8 hours; P P P = .012) and provided a shorter time to initial symptom relief (0.8 vs 3.5 hours; P Conclusions FAST-3 demonstrated that icatibant was effective and generally well tolerated in subjects with acute HAE attacks. Trial Registration Clinicaltrials.gov Identifier: NCT00912093.

Rationale Allergen sensitization is an important risk factor for allergic disease, including allergic rhinitis. This study reports the sensitization status, and efficacy of fexofenadine (FEX), in a subset of children (aged 6–11 yrs) from the Southern Hemisphere with seasonal allergic rhinitis (SAR) enrolled into a large, placebo-controlled, randomized, parallel-group study. Methods For randomization, children required a positive skin prick test to at least one pollen allergen for the current season and concordance to that specific allergen in in vitro IgE testing. Specific IgEs were determined by the Fluoro Enzyme Immuno Assay; positive IgE was defined as IgE class ≥2 (>0.7 kUA/L). Analysis was performed on the modified intention-to-treat (mITT) population, treated with either FEX HCl 30 mg BID or placebo. Efficacy was evaluated as the overall mean change from baseline in 12-hour reflective total symptom score (TSS). Results A subset of 300 subjects (FEX, n=145; placebo, n=155), from 40 centers in Argentina, Chile, Uruguay and South Africa, was analyzed. Sensitization to pollen allergens assessed by plant category showed that grasses were the most common group of allergens (>93%); sensitization to weeds was 8.9% for FEX and 17.8% for placebo; sensitization to trees was 20.5% for FEX and 20.4% for placebo. FEX significantly improved the mean change from baseline in TSS compared with placebo ( p Conclusions In this subset of children from the Southern Hemisphere, grasses were the most common groups of sensitizing allergens. Furthermore, FEX significantly improved the symptoms of SAR in this population of children.

Raised concentrations of cord blood serum (CBs) IgE have previously been demonstrated to reflect a hereditary predisposition for atopy in First World, predominantly white populations. A cross-sectional study of 53 black, 52 white, and 58 mixed race newborn infants and maternal pairs was performed in a multiethnic, mixed First and Third World society. The CBs IgE concentrations were measured with a modification of the standard IgE PRIST, which could reliably determine IgE concentrations to an accuracy of 0.01 kU/L. The black group had the highest geometric mean and median CBs IgE concentrations (0.21; 0.16 kU/L), followed by the white group (0.12; 0.12 kU/L) and the mixed group (0.10; 0.08 kU/L). If those newborn infants with an atopic family history and maternal ascariasis were excluded, the remainder had geometric mean and median CBs IgE concentrations of 0.20; 0.16 kU/L in the black subgroup, followed by values of 0.06; 0.05 kU/L in the mixed subgroup, and 0.05; 0.07 kU/L in the white subgroup. Statistically significant ethnic differences in the median CBs IgE concentrations of these subgroups were demonstrated between the black-white (p less than 0.05) and the black-mixed (p less than 0.005) ethnic groups. A positive family history of atopy influenced the CBs IgE concentrations in the white and mixed groups but not in the black group. Of those newborn infants with a CBs IgE concentration greater than 0.5 kU/L, a family history of atopy was found in 100% of the white newborn infants, in 58.3% of the mixed newborn infants, and only in 14.3% of the black newborn infants. Many of the black newborn infants without a family history of atopy had extremely high CBs IgE concentrations. The influence of maternal ascariasis was equivocal in the mixed group but of no significance in the black group. The high CBs IgE concentrations in the black newborn infants, independent of an atopic family history and maternal ascariasis, suggest that this atopic marker may therefore be of limited use in identifying the "high allergic-risk" newborn infant in black Third World populations who appear to represent a pool of genetic high IgE-responder phenotypes.

Serum samples from 60 adults and 64 children with atopic dermatitis were tested for antistaphylococcal IgE antibodies with RAST discs coupled to cellular proteins from Wood 46 strain S. aureus. Anti- S. aureus IgE antibodies were detected in 19 (29.6%) of the children and 14 (23.3%) of the adult patients. Anti- S. aureus IgE-positive adults had more severe and prolonged disease than those who were negative. Two groups of children comprising 10 who were anti- S. aureus IgE positive and 10 who were negative were compared. Children with anti- S. aureus IgE antibodies had more severe and more extensive disease ( p S. aureus infections ( p p p p