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Biomedical subjects

Paul C Potter

Publications and source records attributed to Paul C Potter.

12 recordsLinked to original sources

Update on sublingual immunotherapy.

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.

Administration, Sublingual↗

Autoantibodies to the high-affinity IgE receptor in children with chronic urticaria.

BACKGROUND: Chronic urticaria (CU) in childhood remains a challenge for investigation, and its etiology is largely unknown. Autoantibodies to the high-affinity IgE receptor (FcepsilonRI) are believed to play a role in the pathogenesis of this disease in adults. OBJECTIVE: To determine the prevalence of autoantibodies to FcepsilonRIalpha on basophils in children with CU vs atopic eczema dermatitis syndrome (AEDS). METHODS: Eighty children with CU were compared with 38 children with AEDS. In addition to complete blood cell counts and total IgE measurements, CAP-RASTs to egg, codfish, soy, milk, and peanut were performed. Stool samples were examined for parasites, and autologous serum skin testing and a functional anti-FcepsilonRIalpha assay were conducted to detect autoantibodies. RESULTS: No significant differences were observed between children with CU and controls in mean basophil or eosinophil counts. Twenty (26%) of 77 children with CU and 31 (82%) of 38 with AEDS had positive CAP-RAST results (P < .001). Only 2.5% of the children with CU and 0% with AEDS had stool samples positive for parasites (P = .005). Anti-FcepsilonRIalpha autoantibodies were positive in 37 (47%) of 78 children with CU and in none of 33 with AEDS. Non-IgG histamine-releasing factors were found in 10 (13%) of 78 children with CU. CONCLUSIONS: Children have a similar prevalence of autoantibodies to the FcepsilonRIalpha as has been previously published for adults. Few have type I allergies, and parasite infestation is also uncommon. Further studies are required to investigate the predictive value of the autoantibodies in these children with respect to clinical profile, requirements for medications other than antihistamines, and remission rates.

Adolescent↗

Allergy practice worldwide: a report by the World Allergy Organization Specialty and Training Council.

In 2004 the World Allergy Organization's Specialty and Training Council conducted a survey of World Allergy Organization (WAO) member societies to obtain information about the status of the specialty of allergy worldwide. Responses were received from 33 countries, representing a population of 1.39 billion people, of whom it was estimated that 22% may suffer from some form of allergic disease. Allergy was reported by 23 respondents to be a certified or accredited specialty in their country, and the number of certified allergists per head of population ranged from 1:25 million to 1:16,000. Allergists were ranked as the fifth most likely clinicians to see cases of allergic asthma, third most likely to see allergic rhinitis, and fourth most likely to see eczema or sinusitis. Nine countries only reported that children with allergic diseases would be seen by a pediatrician with appropriate training. The survey results highlight a pressing need for the development of allergy services worldwide.

Allergy and Immunology↗

Long-term treatment of atopic dermatitis with pimecrolimus cream 1% in infants does not interfere with the development of protective antibodies after vaccination.

OBJECTIVE: We investigated whether treatment of atopic dermatitis with pimecrolimus cream 1% in infants affects the development of a normal antibody response to vaccinations. METHODS: In all, 91 patients participated in a 1-year, open-label extension to a 1-year double-blind study: 76 used pimecrolimus twice daily at the first signs or symptoms of the disease until clearance for 2 years and 15 only in the second year. Serum concentrations of antibodies against tetanus, diphtheria, measles, and rubella were measured at months 18 and 24. RESULTS: The seropositivity rates of 93.6% for tetanus, 88.6% for diphtheria, 88.5% for measles, and 84.4% for rubella were comparable with those reported in literature. Seropositivity was not significantly affected by the use of pimecrolimus at the time of vaccinations (+/- 28 days). CONCLUSIONS: Treatment of atopic dermatitis with pimecrolimus cream 1% in early childhood does not appear to interfere with the development of a normal immune response to vaccinations.

Administration, Cutaneous↗

Long-term control of atopic dermatitis with pimecrolimus cream 1% in infants and young children: a two-year study.

OBJECTIVE AND METHODS: The safety and efficacy of treatment with pimecrolimus cream 1% was evaluated for up to 2 years in infants and young children with atopic dermatitis. Ninety-one patients participated in a 1-year, open-label extension to a 1-year double-blind study. Of these, 76 received pimecrolimus for 2 years. Pimecrolimus was applied twice daily at the first signs or symptoms of the disease until clearance. Outcome measures included the incidence of adverse events and the Eczema Area and Severity Index (EASI). RESULTS: No patient discontinued because of adverse events. The incidence of systemic and skin infections did not increase over time. Over the 2-year period, 2 patients experienced an episode of clinically diagnosed eczema herpeticum. In patients receiving pimecrolimus for 2 years, the mean decrease in EASI score from baseline was 68.7% at 3 months and 70.8% at 24 months. CONCLUSION: Treatment with pimecrolimus cream 1% for up to 2 years was well tolerated and resulted in a marked and sustained improvement of atopic dermatitis.

Administration, Cutaneous↗

Hypersensitivity to airborne spitting cobra snake venom.

BACKGROUND: Although the cytolytic, neurotoxic, and hemolytic actions of snake venoms are well known, the ability of airborne inhaled snake venom of the spitting cobra to induce asthma in snake handlers has not been reported. OBJECTIVE: To report the allergenicity of inhaled snake venom in a snake handler who developed increasing hypersensitivity to airborne venom, produced by spitting cobras during public demonstrations. METHODS: Serum samples were obtained from 2 handlers (our study patient and another snake handler who reported developing wheezing when handling spitting cobras), and desiccated venom was obtained from 9 species to which the handlers were exposed. Serum from an asymptomatic and nonatopic snake handler exposed to the same snake species was used as a control. Phosphate-buffered saline extracts were prepared from the desiccated venom, proteins in the venom extracts were separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and immunoblotting was performed. Inhibition enzyme-linked immunosorbent assays (ELISAs) were performed to demonstrate cross-reactivity. RESULTS: The study patient had never been previously bitten by a cobra. Wheezing occurred rapidly on inhalational exposure and was reversed by inhalation of salbutamol. The patient had developed IgE antibodies to 9 different snake venoms on Western immunoblots, with major IgE binding proteins of 59 to 63 kDa and 8 to 15 kDa. The cross-reactive nature of the IgE epitopes in the venoms in the different species was also confirmed by 50% inhibition of IgE binding in an ELISA by preincubation with unrelated species. Life-threatening sensitivity of the patient was sustained after a long period of avoidance. CONCLUSIONS: We propose that aerosolized snake venom be considered a new potential source of allergens that may result in anaphylaxis on subsequent exposure. Further studies of the development of specific IgE sensitization following snakebites and the risks of such sensitization should be conducted on snake handlers, particularly those who demonstrate the spitting species.

Administration, Inhalation↗

Efficacy and safety of levocetirizine on symptoms and health-related quality of life of children with perennial allergic rhinitis: a double-blind, placebo-controlled randomized clinical trial.

BACKGROUND: This randomized study examined the efficacy and safety of levocetirizine in pediatric patients with perennial allergic rhinitis. Health-related quality of life (HRQL) was also investigated, which is particularly relevant in children because of the effects of rhinitis on learning, social activities, and comorbidity. OBJECTIVE: To evaluate the effect of levocetirizine on the Total 4 Symptoms Score, the 50% response rate, the Pediatric Rhinitis Quality of Life Questionnaire (PRQLQ), and investigators' global evaluation of symptom improvement. METHODS: Double-blind, placebo-controlled, randomized, multicenter trial of levocetirizine, 5 mg once daily for 4 weeks, in 306 children with perennial allergic rhinitis aged 6 to 12 years. There were 154 children in the levocetirizine arm and 152 in the placebo group who completed daily diary cards, and the PRQLQ and investigators' global evaluations were conducted at 3 visits. RESULTS: The levocetirizine group showed a significant improvement in 2-week and 4-week Total 4 Symptoms Score compared with placebo (P = .001 and P = .008, respectively). The 50% response rate for the first 2 weeks was 12.3% for the levocetirizine group compared with 3.9% for the placebo group (P = .01). The investigators' global evaluation also favored levocetirizine, because 57.1% of the children in the levocetirizine group were considered markedly or moderately improved compared with 44.7% in the placebo group. Levocetirizine also provided a significantly greater HRQL improvement than placebo at 2 weeks (P = .01), and the frequency of adverse events did not differ significantly from those seen in the placebo group. CONCLUSION: The study confirmed the efficacy of levocetirizine in relieving symptoms of perennial allergic rhinitis in children between 6 and 12 years of age. A HRQL benefit greater than placebo was shown. The treatment was well tolerated.

Cetirizine↗

Low prevalence of latex sensitivity in South African spina bifida children in Cape Town.

Spina bifida children have a high prevalence of latex allergy in studies reported from Europe and the USA. This study investigated the prevalence of latex allergy in a cohort of 24 spina bifida children at the Red Cross Children's Hospital from Cape Town, South Africa. The children were investigated using a detailed questionnaire, skin prick tests (ALK-Abello), ImmunoCap RASTs, Western blotting and ELISA, using the purified latex proteins Hev b1 and Hev b3 and whole latex preparation. A low overall prevalence of latex sensitization of 16.7% was found in the children. Children who were sensitive reacted to water insoluble to Hev b1 and Hev b3 proteins. The low prevalence of latex sensitization in the South African children may not be entirely explained by stringent latex avoidance. The children were from a low socioeconomic social status and 'hygiene' and other factors should be considered.

Adolescent↗

Qualitative and quantitative evaluation of bird-specific IgG antibodies.

BACKGROUND: Exposure to organic dust produced by birds often gives rise to an immune response, e.g. IgG antibodies, but intense exposure can lead to high concentrations of IgG antibodies and the development of allergic alveolitis, often known as "bird fancier's lung". The aim of this study was to establish the distribution of bird-specific IgG antibodies in exposed and nonexposed individuals and compare a nonquantitative and quantitative method in evaluating raised levels of IgG antibodies. METHODS: Sera were collected in Sweden and South Africa and levels of IgG antibodies specific to pigeon, budgerigar and parrot antigens were quantified using the UniCAP system. Results were compared to the precipitation in gel assay. The IgG antibody values of symptomatic patients without precipitating antibodies (non-PP group; n = 51) and patients with precipitating antibodies (PP group; n = 34) were analyzed and compared to nonexposed asymptomatic blood donors (BD group; n = 73) and environmentally exposed pigeon breeders (n = 11). RESULTS: The IgG antibody response of the analyzed groups in Sweden and South Africa did not vary significantly from each other. IgG antibody responses were the strongest to pigeon antigens with clear increased IgG antibody levels in the PP group [geometric mean (GM) 603 mg/l] compared to the non-PP (GM 6.9 mg/l) and BD group (GM 5.0 mg/l). Threshold values, calculated as the GM value from the BD group plus 3 standard deviations (99% confidence interval), were 9.8, 10.8 and 10.0 mg/l for pigeons, budgerigars and parrots, respectively. Comparison of the two methods resulted in a good concordance with a level of agreement of 94.1% (kappa statistic = 0.83). CONCLUSIONS: The UniCAP system for the detection of bird-specific IgG antibodies is a highly reproducible, generally available, quantitative method for routine diagnostic testing and monitoring of exposed subjects with a very high level of agreement to the precipitating gel assay.

Alveolitis, Extrinsic Allergic↗

Bronchial hyper-responsiveness and atopy in urban, peri-urban and rural South African children.

Twenty years ago, the prevalence of atopic sensitization and bronchial hyper-responsiveness (BHR) in Xhosa children in a rural location in South Africa was very low. The aim of this study was to document the current prevalence of these two indices by comparing traditional rural Xhosa children, recently urbanized Xhosa children and established city white children, and to consider factors that may account for the observed increase in all of these groups. One thousand four hundred and fifty-seven school children aged 10-14 years from the rural Transkei, from a recently urbanized peri-urban area and from urban Cape Town areas were studied using a questionnaire. Four hundred and eighteen children had histamine challenges, and 492 tests for atopy were also conducted. As determined by bronchial challenge with histamine, 17% of rural and 34.4% of recently urbanized Xhosa children had increased BHR, a marked increase from the 0.03% and 3.17% prevalence of increased BHR previously found using the exercise challenge. The prevalence of increased BHR in white urban children was 33%. Sensitization to one or more aero-allergens, as indicated by CAP RAST tests, was present in 36.6% of the rural Xhosa children with normal BHR and in 62.5% of those with increased BHR, a striking increase from that of previous studies. Atopic sensitization to one or more aero-allergens, as indicated by a skin prick test (SPT), was found in 42.3% of the recently urbanized Xhosa children and 45% of urbanized white children. We have also documented sensitization to house dust mites in the rural Xhosa children for the first time. Passive cigarette smoking was not identified as a risk factor for increased BHR or atopy. Wood smoke in the indoor environment did not play a role in the rural Xhosa children's BHR. Ascaris infection does not appear to play any modifying role in the development of increased BHR in the rural or urban children. We have found that increases in BHR in the rural and recently urbanized Xhosa children develop independently of increases in atopy. Our results challenge the 'hygiene' hypothesis as a complete explanation for the recent dramatic worldwide increases in allergic diseases.

Adolescent↗

Long-term management of atopic dermatitis in infants with topical pimecrolimus, a nonsteroid anti-inflammatory drug.

BACKGROUND: Pimecrolimus cream 1% (Elidel, SDZ ASM 981), a nonsteroid selective inhibitor of inflammatory cytokines, is effective in the treatment of atopic dermatitis (AD). In this study we compared early intervention with pimecrolimus cream with treatment with a vehicle control. OBJECTIVE: The purpose of this investigation was to assess whether early treatment in infants of AD signs/symptoms with pimecrolimus could influence long-term outcome by preventing disease flares. METHODS: In this 1-year, double-blind controlled study, 251 infants aged 3 to 23 months with AD were randomized 4:1 to a pimecrolimus-based regimen (n = 204) or a conventional treatment regimen (n = 47). Both groups used emollients for dry skin. Early AD signs and symptoms were treated either with pimecrolimus cream to prevent flares or, in the control group, with vehicle. Vehicle was used to maintain blinding conditions. In the event of flares, moderately potent corticosteroid was permitted in both groups. The primary efficacy end point was the incidence of flares at 6 months. RESULTS: Pimecrolimus significantly reduced the incidence of flares compared with control treatment (P <.001), with 67.6% versus 30.4% of patients completing 6 months with no flare and 56.9% versus 28.3% completing 12 months with no flare. Overall corticosteroid use was substantially lower in the pimecrolimus group: 63.7% versus 34.8% of patients did not use corticosteroids at all during the study. Pimecrolimus was also more effective than control treatment in the long-term control of pruritus and the signs of AD. There were no clinically significant differences in incidence of adverse events between the 2 treatment groups. CONCLUSIONS: Treatment with pimecrolimus of early signs and symptoms significantly modified the disease course in infants by reducing the incidence of flares and improving overall control of AD. Pimecrolimus was safe and well tolerated.

Anti-Inflammatory Agents, Non-Steroidal↗