Allergic rhinits: impact on quality of life of adolescents.

SUMMARY: Adolescence is one of the most rapid phases of human development, in which biological maturity precedes psychosocial maturity. Rhinoconjunctivitis (ARC) is present in around 15 percent of 13-14-year-old children, which indicates a higher prevalence when compared with 6-7-year-old children (8.5 percent). During childhood (0-10 years) prevalence of Allergic Rhinitis (AR) is higher among males compared to females. Quite the reverse, during adolescence (11-17 years) females display higher prevalence of AR compared to males. However, when they reach adulthood (18-79 years), there is no difference in prevalence between genders. AR and ARC have significant physical and mental impacts on the QoL of adolescents and their parents. Apart from de adverse effects of first generation antihistamines, which include sedating effects, AR-ARC leads to school absences and poorer performance due to distraction, fatigue and irritability. The mobile technology facilitates an innovative investigatory approach to better and more precisely characterize allergy symptoms and their association with other allergic diseases. The success of treatment lies in the partnership between adolescents with AR and mobile technology, allowing them to have more information both on the disease and treatment. Adolescence is a special period in which AR is highly prevalent with some sex-dependent differences. There are also peculiarities on how AR affects QoL of adolescent patients.

Renal safety after one year of sofosbuvir-based therapy for chronic hepatitis C: A Brazilian "real-life" study.

WHAT IS KNOWN AND OBJECTIVE: Sofosbuvir(SOF)-based regimens have been administrated with excellent efficacy in chronic hepatitis C. Few uncontrolled ("real-life") studies consider the assessment of renal function when evaluating their post-treatment outcomes. This study aims to evaluate renal biomarkers in a "real-life" experience with chronic hepatitis C patients treated with SOF therapy in a long-term follow-up. METHODS: Serum and urinary biomarkers were analysed before, at the end of therapy (EoT), after 12 weeks (sustained virological response-SVR) and one year (1y) post-treatment. Patients were categorized according to baseline glomerular filtration rate (GFR-cut-off 45 mL/min/1.73 m2 ). RESULTS: Ninety-four patients with a mean age of 59.9 ± 8.5 years were included; 98.9% of patients reached SVR. Significant improvement in renal biomarkers was observed in patients with GFR ≥45 mL/min/1.73 m2 , as indicated by a progressive increase in mean GFR values until 1y. No evidence of tubular dysfunction was identified. Patients with baseline GFR <45 mL/min/1.73 m2 did not experience alterations in renal biomarkers; however, a mean change of +10.7 in GFR values was observed. We noticed significant upper stage transition in the CKD classification, and 58.7% of patients achieved G1 stage at 1y (P < .0001). WHAT IS NEW AND CONCLUSION: In a "real-life experience" of a Brazilian centre, SOF therapy appears to guarantee renal safety for patients with chronic hepatitis C followed until one year after treatment.

National clinical practice guidelines for allergen immunotherapy: An international assessment applying AGREE-II.

BACKGROUND: Since 1988, numerous allergen immunotherapy guidelines (AIT-GLs) have been developed by national and international organizations to guide physicians in AIT. Even so, AIT is still severely underused. OBJECTIVE: To evaluate AIT-GLs with AGREE-II, developed in 2010 by McMaster University methodologists to comprehensively evaluate GL quality. METHODS: Allergist, from different continents, knowledgeable in AIT and AGREE-II trained were selected into the project team. The project received methodologists' guidance. AIT-GLs in any language were sought from 1980 to 2016; AIT-GLs were AGREE II-evaluated by at least 2 team members, independently; discrepancies were resolved in a second round, by team discussion or methodologists' consulting. RESULTS: We found 31 AIT-GLs (15 post-2010), ranging from local consensus reports to international position papers (EAACI, AAAAI-ACAAI, WAO). Pre-2010 GLs scored 1.6-4.6 (23%-67%) and post-2010 GLs scored 2.1-6 (30%-86%), on a 7-point Likert scale. The highest scores went to: German-Austrian-Swiss (6.0), Mexican (5.1), and the AAAAI/ACAAI AIT-GL (4.7). These were also the only 3 GLs that received "yes" of both evaluators to the item: "I would recommend this GL for use." The domains of "Stakeholder involvement" and "Rigor of Development" only scored 3/7, and "Applicability" scored the lowest. Strikingly, newer GLs only scored clearly better in "Editorial independence" and "Global evaluation." CONCLUSIONS: In AIT-GLs, there is still a lot of room for improvement, especially in domains crucial for the dissemination. For some GLs, the "Scientific rigor" domain flawed. When resources are limited, transculturizing a high-quality GL might be preferable over developing a GL from zero. Our study and AGREE-II could help to select the best candidate. CLINICAL IMPLICATIONS: We here evaluate allergen immunotherapy guideline (AIT-GL) quality. Only high-quality AIT-GLs should be consulted for AIT management decisions. In low-resource settings, transculturization of these is preferred over developing low-quality guidelines.

Sleep-related disorders in Latin-American children with atopic dermatitis: A case control study.

BACKGROUND: Atopic dermatitis (AD) has been associated with impairment of sleep. The aim of this study was to evaluate sleep disorders in AD Latin-American children (4-10 years) from nine countries, and in normal controls (C). METHODS: Parents from 454 C and 340 AD children from referral clinics answered the Children Sleep Habits Questionnaire (CSHQ), a one-week retrospective 33 questions survey under seven items (bedtime resistance, sleep duration, sleep anxiety, night awakening, parasomnias, sleep-disordered breathing and daytime sleepiness). Total CSHQ score and items were analysed in both C and AD groups. Spearman's correlation coefficient between SCORAD (Scoring atopic dermatitis), all subscales and total CSHQ were also obtained. RESULTS: C and AD groups were similar regarding age, however, significantly higher values for total CSHQ (62.2±16.1 vs 53.3±12.7, respectively) and items were observed among AD children in comparison to C, and they were higher among those with moderate (54.8%) or severe (4.3%) AD. Except for sleep duration (r=-0.02, p=0.698), there was a significant Spearman's correlation index for bedtime resistance (0.24, p<0.0001), sleep anxiety (0.29, p<0.0001), night awakening (0.36, p<0.0001), parasomnias (0.54, p<0.0001), sleep-disordered breathing (0.42, p<0.0001), daytime sleepiness (0.26, p<0.0001) and total CSHQ (0.46, p<0.0001). AD patients had significantly higher elevated body mass index. CONCLUSION: Latin-American children with AD have sleep disorders despite treatment, and those with moderate to severe forms had marked changes in CSHQ.

Sleep disorders in Latin-American children with asthma and/or allergic rhinitis and normal controls.

BACKGROUND: Asthma and/or allergic rhinitis have been associated with sleep disorders. The aim of this study was to evaluate sleep disorders in Latin-American children (4-10 years) from nine countries, with persistent asthma (A) and/or allergic rhinitis (AR) and in normal controls (C). METHODS: Parents from 454 C children and 700 A and/or AR children followed up in allergy reference clinics completed the Children's Sleep Habits Questionnaire (CSHQ) which is a retrospective one-week questionnaire composed of 33 questions composed of seven subscales (bedtime resistance, sleep duration, sleep anxiety, night wakings, parasomnias, sleep-disordered breathing and daytime sleepiness). The total scale of CSHQ and the subscales were compared between groups C and A+AR, A (n=285) vs. AR (n=390), and between controlled A (CA, n=103) vs. partially controlled/uncontrolled A (UA, n=182). RESULTS: The comparison between C and A+AR showed no significant differences in age (6.7 years vs. 7.0 years, respectively), mean Body Mass Index and total scale of CSHQ (53.3 vs. 63.2, respectively) and the subscales were significantly higher in the A+AR group. Comparison between groups A and AR, except for sleep anxiety, showed significantly higher values for CSHQ total scale (66.9 vs. 61.0, respectively) and subscales for group A. The UA group showed significantly higher values for total CSHQ scale and subscales in comparison to CA (71.1 vs. 59.4, respectively). CONCLUSIONS: Latin-American children with asthma and/or allergic rhinitis showed sleep disorders identified by the CSHQ when compared to normal controls. Despite being treated, asthma causes sleep impairment, especially when uncontrolled.

Similar biological activity in skin prick test for Oralair® (8200 BAU) and Grazax® (6200 BAU) reinforces effective SLIT dosing level.

In Europe, allergen extracts are standardized based on skin prick wheal size in 20-30 allergic subjects. To understand the biological activity of clinically effective Sublingual immunotherapy, we used this method to determine the biological activity of solution and tablet Timothy grass pollen (TIM) extracts, compared to an FDA-approved extract (Reference) of 10 000 BAU/ml. Blinded, quadruplicate skin prick tests with concentrate and three serial half-log dilutions allowed the construction of a semilogarithmic regression line per extract. Bioequivalent allergy units (BAU) values were obtained from the comparison with reference. Extracts and dilutions showed a neat linear dose response (all: R2 > 0.98) in 33 rhinitis patients. Relative potencies: Staloral® 12 000 BAU/ml, Soluprick® 10 300 BAU/ml, Oralair® 8200 BAU, and Grazax® 6200 BAU. Even though all extract concentrates differed in wheal size (P = 0.01-0.001), Grazax® producing a 25% smaller wheal size than Oralair® , and the biological activity of these clinically effective TIM tablets led in the same range (6200-8200 BAU; 0.92-1.23 cm2 ). SLIT dose-finding studies for other pollens might start with allergen extracts producing 1.1 cm2 wheal surface.

Molecular-based diagnosis of respiratory allergic diseases in children from Curitiba, a city in Southern Brazil.

BACKGROUND: Prevalence of respiratory allergic diseases has increased worldwide. Identification of the aeroallergens involved in allergenic sensitisation is important for diagnosis, treatment and prevention. OBJECTIVE: To verify the molecular pattern of sensitisation to aeroallergens in patients with allergic respiratory diseases using microarray technique for specific IgE antibody detection. METHODS: Cross-sectional study of 101 children with allergic rhinitis was followed in an outpatient clinic. All patients had positive skin prick tests (SPT) to at least one of the following antigens: Dermatophagoides pteronyssinus, Blomia tropicalis, Blattella germanica, Lolium multiflorum, and dog and cat epithelium. Serum specific IgE antibodies (sIgE) to mites, animal epithelia, fungi, cockroach and pollens components were determined by ImmunoCAP ISAC. RESULTS: sIgE to group 1 and 2 mite allergens showed higher positive rates: Der p 1 (74.2%), Der p 2 (73.3%), Der f 1 (74.2%), Der f 2 (72.3%). sIgE to animal epithelia were less frequent, Can f 1, Can f 2, Can f 3 in 4.9%, 2.9%, 1.9% respectively and Fel d 1, Fel d 2, Fel d 4 in 16.8%, 0.9% and 1.9%. respectively. Sensitisation to fungi and cockroach were rare, except for Bla g 7, to which 16.8% were positive. There was no significant recognition for tree pollens group. For grass, sIgE were detected to Cyn d 1 in 16.8%, Phl p 1 and Phl p 4 in 14.8% and 12.9%, respectively. CONCLUSION: Knowing that the pattern of allergic sensitisation varies according to environment and population, our results reinforce the need for local studies, using molecular-based diagnosis.

Allergic rhinitis in preschool children from Southern Brazil.

There are few published studies on prevalence of allergic rhinitis in preschool children. The aims of this study were to verify the prevalence, clinical characteristics, and treatment of allergic rhinitis (AR) symptoms in the first year of life adding supplementary questions to the EISL instrument. A cross-sectional study used Phase III EISL written questionnaire in addition to modified allergic rhinitis ISAAC questions. One thousand and three parents of infants answered the questionnaire: 484 (48.3%) had at least one sneezing, or a runny or blocked nose episodes without cold or flu in the first year of life. A quarter of infants had recurrent wheezing (≥3 episodes) and more frequent in the presence of AR symptoms. Physician diagnosis of AR and the use of intranasal steroids and both antihistamines and intranasal steroids were more common among those infants with AR symptoms. The prevalence of AR symptoms was high and starting early in life.

Anaphylaxis in Latin American children and adolescents: the Online Latin American Survey on Anaphylaxis (OLASA).

OBJECTIVES: To identify the main clinical manifestations, triggers, and treatment of severe allergic reactions (SAR) in children and adolescents (n=191, up to 18 years of age) seen by allergologists and registered in the Online Latin American Survey of Anaphylaxis (OLASA). RESULTS: 53.0% of the patients were males and the aetiological agent was identified in 85.5% of them as follows: foods (36.1%), drugs (27.7%), and insect stings (26.2%). The most common symptoms during an acute episode were cutaneous (94.2%), and respiratory (78.5%). Most patients were treated in emergency setting, yet only 34.6% received parenteral epinephrine and 14.3% had to be hospitalised. CONCLUSION: Cutaneous symptoms ranked the order of clinical presentation of SAR. Food was the main triggering agent in the younger cases and insect sting and drugs in the adolescents. Treatment provided for SAR was not appropriate. It is necessary to improve educational programmes in order to enhance the knowledge on this potentially fatal emergency.

Validation of a questionnaire for epidemiologic studies of wheezing in infants.

Large international studies on asthma and allergies in childhood have found notorious variation in prevalence and temporal trend among countries. However, there is no international studies on the epidemiologic characteristics of wheezing in the first year of life. The aim of this study was to validate a questionnaire to assess the prevalence of wheezing in infants from Latin America, Spain, and Portugal. This study was undertaken in pediatric emergency rooms (PER). A randomized sample of parents visiting PER because lower respiratory illness, answered a questionnaire on wheezing developed by the International Study of Wheezing in Infants. During visit, all infants were examined by one of the authors (blind) who reported, or not, the presence of wheezing on chest auscultation. Sensitivity, specificity, predictive positive value, predictive negative value, and agreement level were calculated from parent and physician reports. Two hundred and nine infants aged 12-15 months participated in the study. Fifty-six parents reported current wheezing and 43 were confirmed by physician; 153 parents did not report current wheezing and 146 had not wheezing at physical examination (agreement = 0.74, CI 95% 0.64-0.85). This questionnaire showed high sensitivity (86%), specificity (91.8%), positive predictive value (76.8%) and predictive negative value (95.4%). Regardless of previous experience with wheezing episodes, parents can reliably inform when their infants are currently wheezing. A simple and convenient questionnaire confirmed by physical examination produce an accurate tool to asses the prevalence of asthma symptoms in infants.

Changes in the prevalence of asthma and allergic diseases among Brazilian schoolchildren (13-14 years old): comparison between ISAAC Phases One and Three.

The present study is aimed to describe the changes in the prevalence of symptoms of asthma, rhinitis and eczema among Brazilian adolescents (AD, 13-14 years old) between Phases 1 and 3 of the International Study of Asthma and Allergies in Childhood (ISAAC). The prevalence of self-reported symptoms of asthma, rhinitis and eczema in AD from five Brazilian cities (Curitiba, Porto Alegre, Recife, Salvador and São Paulo), obtained during ISAAC Phase 1 (n = 15 419) and Phase 3 (n = 15 684), was compared to determine the trend of prevalence in a 7-year interval. There was a trend to reduction in the current prevalence of wheezing and increasing of nocturnal cough when averaging figures from the five cities. The prevalence of wheezing in the last 12 months was 27.7 vs. 19.9% (p < 0.01); asthma ever 14.9 vs. 14.7% (p > 0.05); severe episode of wheezing 5.2 vs. 5.2%; nocturnal cough 32.6 vs. 34.9% (p < 0.01); exercise wheezing 23.6 vs. 23.0% (p > 0.05) and awake with wheezing 11.8 vs. 11.2% (p > 0.05). Similar things were observed with the prevalence of current symptoms of rhinitis and eczema. In Brazil, there was a small but significant mean decrease in the prevalence of two asthma-related symptoms, wheezing and nocturnal cough, though this trend was not consistent in the surveyed cities. The prevalence of asthma symptoms in Brazil, despite its mean trend to a decrease, is still one of the highest in Latin America.

Increase in prevalence of rhinoconjunctivitis but not asthma and atopic eczema in teenagers.

OBJECTIVE: We sought to assess changes in the prevalence of asthma and other allergic diseases in schoolchildren of Curitiba between 1995 and 2001. METHODS: Schoolchildren (aged 13-14) were evaluated by a self-reported written questionnaire of ISAAC protocol for symptoms of asthma and allergic diseases. The diagnoses of asthma, rhinoconjunctivitis and atopic eczema were considered according to the ISAAC protocol. Probable asthma was considered: more than 4 attacks of wheezing in the last 12 months; 1 to 3 attacks of wheezing in the last 12 months with dry cough at night, and/or with sleep disturbance due to wheezing, and/or with wheezing after exercise. The data obtained in 2001 were compared with the data obtained in 1995 for the same age group. RESULTS: We evaluated 2,946 schoolchildren in 1995 and 3.628 in 2001. The prevalence of symptoms of asthma, probable asthma, rhinoconjunctivitis and eczema in 1995 and 2001 was 18.4% and 18.7%, 11.6% and 12.4%, 14.2% and 17.2%, 3.8% and 3.7%, respectively. There was a 23.7% increase in the prevalence of rhinoconjunctivitis symptoms (p < 0.05). CONCLUSIONS: The prevalence of symptoms of asthma, probable asthma and eczema did not change over the past 6 years but a significant increase of the rhinoconjunctivitis symptoms was detected.

Intravenous vitamin C as a chemotherapy agent: a report on clinical cases

A series of seven cases are presented in which intravenous vitamin C has been used as antineoplastic agent in the treatment of different types of cancers. The cancers cases reviewed are the following: Renal cell carcinoma (2), Colorectal cancer (1), Pancreatic cancer (1), Non-Hodgkin's lymphoma (2) and breast cancer (1). Toxic reactions were not observed at these high doses of intravenous Vitamin C. All patients were prescreened for Glucose 6--phosphate dehydrogenase deficiency before administering intravenous Vitamin C in order to prevent hemolysis

Intravenous ascorbic acid: protocol for its application and use

High dose intravenous(i.v.) ascorbic acid (AA) has been used as therapy for infectious disease from bacterial and viral origin and adjuvant therapy for cancer. In this publication we describe a clinical protocol that has been developed over the past twenty years utilizing high dose i.v. AA as therapy for cancer. This includes principles of treatment, rationale, baseline workup, infusion protocol, precautions and side effects.

[Inflammatory mediators, cell counts in nasal lavage and computed tomography of the paranasal sinuses in atopic children] / Mediadores inflamatórios, citograma em lavado nasal e tomografia computadorizada de seios paranasais em crianças atópicas.

OBJECTIVE: The aims of this study were to evaluate inflammatory cells, the profile of inflammatory mediators in nasal lavage (NL), and the involvement of the paranasal mucosa in atopic infants with no symptoms of sinusitis. METHODS: 48 atopic patients with allergic rhinitis (AR), and 33/48 patients with asthma were studied; the control group consisted of 13 nonatopic children. Those individuals with acute, chronic or recurrent sinusitis were excluded. The involvement of the paranasal mucosa was assessed by coronal computed tomography (CT) and graded by a standard protocol (0-30). A CT score greater than or equal to 12 indicated extensive involvement. Nasal lavage was used to quantify total and differential nasal cell counts. An aliquot of the supernatant was used for determining inflammatory mediators: interleukin-8 (IL-8), myeloperoxidase (MPO), and eosinophil cationic protein (ECP). Albumin was used as a marker for increased vascular permeability. These measurements were performed on all of the atopic patients and in 6/13 patients in the control group. The three groups were submitted to spirometry and complete blood cell count. RESULTS: Extensive involvement of the paranasal mucosa was observed in 7/33 (21%) of asthmatic patients (Group I) and 2/15 (13%) of those with allergic rhinitis (Group II). The highest CT score in the control group (Group III) was 7. Total cell and eosinophil count/ml and albumin concentration in nasal fluid were higher in asthmatic patients whose CT score was greater than 12. Interleukin-8 concentration, number of neutrophils and epithelial cells/ml in nasal fluid were similar in the three groups. A positive correlation between CT score, peripheral blood eosinophilia, number of eosinophils/ml and eosinophil cationic protein concentration was found in the nasal fluid of atopic children (n=48). There was an association between number of neutrophils and titers of interleukin-8 and myeloperoxidase, and between interleukin-8 and eosinophil count. CONCLUSIONS: in asthmatic patients with no symptoms of sinusitis, the extensive involvement of the paranasal mucosa is associated with blood and nasal lavage eosinophilia and cellular activation. Neutrophil infiltration and activation were not related to increased involvement of the paranasal mucosa.

[Clinical findings of sensitivity to analgesics and nonsteroidal antiinflammatory drugs]. / Achados clínicos da sensibilidade a analgésicos e antiinflamatórios não-hormonais.

BACKGROUND: Analgesics (ANA) and nonsteroidal antiinflammatory drugs (NSAID) may simulate an allergic reaction or aggravate asthma and urticaria. OBJECTIVE: The aim of this study was the analysis of the clinical findings in patients sensitive to ANA/NSAID. METHODS AND SUBJECTS: The charts of 183 patients with history of reacting to these drugs were retrospectively analysed. RESULTS: There were 93 (51%) females and 90 (49%) males; 63 (34%) were aged 15 years or less. Females predominate in the age group older than 15 years (p = 0,02). The age by the time of the first reaction varied from 7 months to 65 years (median 15 years). Skin tests to inhalant allergens were positive to at least one antigen in 100/138 patients (72%). Clinical presentation was angioedema (86%); urticaria (39%); systemic reaction (30%); nasal and ocular (15%); and asthma (14%). The frequency of symptoms was not related to age. Family history of ANA/NSAID sensitivity was present in 3.8% of patients. Associated diseases were rhinitis (55%), chronic urticaria (47%), asthma (37%) and conjuntivitis (18%). Among asthmatics 16 (23,5%) had had attacks with ANA/NSAID. Nine non asthmatics (7.7%) had had bronchospasm as clinical presentation. This difference was statistically significant. Repeated reactions occurred in 107 (58%) patients. CONCLUSIONS: Sensitivity to ANA/NSAID was frequent in atopics; children and adults responded similarly; reactions were more common in adult females; palpebral angioedema was the most frequent clinical presentation; bronchosphasm was usually seen in asthmatics and most patients reacted repeatedly to different drugs.