Allergen sensitization linked to climate and age, not to intermittent-persistent rhinitis in a cross-sectional cohort study in the (sub)tropics.

BACKGROUND: Allergen exposure leads to allergen sensitization in susceptible individuals and this might influence allergic rhinitis (AR) phenotype expression. We investigated whether sensitization patterns vary in a country with subtropical and tropical regions and if sensitization patterns relate to AR phenotypes or age. METHODS: In a national, cross-sectional study AR patients (2-70 y) seen by allergists underwent blinded skin prick testing with a panel of 18 allergens and completed a validated questionnaire on AR phenotypes. RESULTS: 628 patients were recruited. The major sensitizing allergen was house dust mite (HDM) (56%), followed by Bermuda grass (26%), ash (24%), oak (23%) and mesquite (21%) pollen, cat (22%) and cockroach (21%). Patients living in the tropical region were almost exclusively sensitized to HDM (87%). In the central agricultural zones sensitization is primarily to grass and tree pollen. Nationwide, most study subjects had perennial (82.2%), intermittent (56.5%) and moderate-severe (84.7%) AR. Sensitization was not related to the intermittent-persistent AR classification or to AR severity; seasonal AR was associated with tree (p < 0.05) and grass pollen sensitization (p < 0.01). HDM sensitization was more frequent in children (0-11 y) and adolescents (12-17 y) (subtropical region: p < 0.0005; tropical region p < 0.05), but pollen sensitization becomes more important in the adult patients visiting allergists (Adults vs children + adolescents for tree pollen: p < 0.0001, weeds: p < 0.0005). CONCLUSIONS: In a country with (sub)tropical climate zones SPT sensitization patterns varied according to climatological zones; they were different from those found in Europe, HDM sensitization far outweighing pollen allergies and Bermuda grass and Ash pollen being the main grass and tree allergens, respectively. Pollen sensitization was related to SAR, but no relation between sensitization and intermittent-persistent AR or AR severity could be detected. Sensitization patterns vary with age (child HDM, adult pollen). Clinical implications of our findings are dual: only a few allergens -some region specific- cover the majority of sensitizations in (sub)tropical climate zones. This is of major importance for allergen manufacturers and immunotherapy planning. Secondly, patient selection in clinical trials should be based on the intermittent-persistent and severity classifications, rather than on the seasonal-perennial AR subtypes, especially when conducted in (sub)tropical countries.

In the (sub)tropics allergic rhinitis and its impact on asthma classification of allergic rhinitis is more useful than perennial-seasonal classification.

BACKGROUND: Two different allergic rhinitis (AR) symptom phenotype classifications exist. Treatment recommendations are based on intermittent-persistent (INT-PER) cataloging, but clinical trials still use the former seasonal AR-perennial AR (SAR-PAR) classification. This study was designed to describe how INT-PER, mild-moderate/severe and SAR-PAR of patients seen by allergists are distributed over the different climate zones in a (sub)tropical country and how these phenotypes relate to allergen sensitization patterns. METHODS: Six climate zones throughout Mexico were determined, based on National Geographic Institute (Instituto Nacional de Estadística y Geografía) data. Subsequent AR patients (2-68 years old) underwent a blinded, standardized skin-prick test and filled out a validated questionnaire phenotyping AR. RESULTS: Five hundred twenty-nine subjects participated in this study. In the tropical zone with 87% house-dust mite sensitization, INT (80.9%; p < 0.001) and PAR (91%; p = 0.04) were more frequent than in the subtropics. In the central high-pollen areas, there was less moderate/severe AR (65.5%; p < 0.005). Frequency of comorbid asthma showed a clear north-south gradient, from 25% in the dry north to 59% in the tropics (p < 0.005). No differences exist in AR cataloging among patients with different sensitization patterns, with two minor exceptions (more PER in tree sensitized and more PAR in mold positives; p < 0.05). CONCLUSION: In a (sub)tropical country the SAR-PAR classification seems of limited value and bears poor relation with the INT-PER classification. INT is more frequent in the tropical zone. Because PER has been shown to relate to AR severity, clinical trials should select patients based on INT-PER combined with the severity cataloging because these make for a better treatment guide than SAR-PAR.

Over diagnosis of persistent allergic rhinitis in perennial allergic rhinitis patients: a nationwide study in Mexico.

BACKGROUND: Allergic rhinitis (AR) symptom phenotypes have been described, and two different classifications exist. The former classification, seasonal versus perennial AR (SAR-PAR), and the Allergic Rhinitis and Its Impact on Asthma (ARIA) classifications, intermittent (INT) versus persistent (PER; ≥4 days/wk and ≥4 consecutive weeks) and mild versus moderate/severe. ARIA cataloging of INT-PER is based on the patient's description of the frequency of symptoms. This study was designed to (1) describe the epidemiology of these two AR classifications and relate them to one another and to a visual analog severity scale (VAS) and (2) describe how the cataloging of these classifications differs between patients and allergists. METHODS: Skin-prick test-positive AR patients seen nationwide by Mexican allergists completed a validated questionnaire cataloging AR. They recorded demographic data and AR severity on a VAS. The patients' physicians were also asked to classify the AR phenotypes. RESULTS: Of the patients, 56.5% had INT and 82.2% had PAR and moderate-severe (84.7%) AR. However, 57% of the INT-PAR patients were misdiagnosed as PER-PAR by their physicians. PER patients had more severe disease with a longer clinical history, more PAR, nose and eye symptoms, and a higher VAS score, and only 7% had mild symptoms. VAS values ≥7.45 relate to PER (sensitivity, 68%; specificity, 65%). VAS ≤6.2 indicated mild and ≥6.4 indicated moderate-severe AR. Similar to the adults, in the 2- to 11 year and 12- to 17-year age groups perennial, INT, and moderate-severe AR was the most frequent finding, but the children had more INT (p < 0.01) and mild (p < 0.03) symptoms, less SAR (p = 0.03), and more physician-diagnosed asthma (p < 0.05). Public health care (PHC) patients had more INT (p = 0.016). CONCLUSION: In the PAR group, the physicians' classification of INT-PER often goes astray. PER overdiagnoses might affect treatment decisions because PER is a more severe phenotype. VAS is useful to evaluate severity. In Mexican AR patients, rhinitis symptom phenotypes differ according to age and between private and PHC system patients.

Regorafenib effects on human colon carcinoma xenografts monitored by dynamic contrast-enhanced computed tomography with immunohistochemical validation.

OBJECTIVE: To investigate dynamic contrast-enhanced computed tomography for monitoring the effects of regorafenib on experimental colon carcinomas in rats by quantitative assessments of tumor microcirculation parameters with immunohistochemical validation. MATERIALS AND METHODS: Colon carcinoma xenografts (HT-29) implanted subcutaneously in female athymic rats (n = 15) were imaged at baseline and after a one-week treatment with regorafenib by dynamic contrast-enhanced computed tomography (128-slice dual-source computed tomography). The therapy group (n = 7) received regorafenib daily (10 mg/kg bodyweight). Quantitative parameters of tumor microcirculation (plasma flow, mL/100 mL/min), endothelial permeability (PS, mL/100 mL/min), and tumor vascularity (plasma volume, %) were calculated using a 2-compartment uptake model. Dynamic contrast-enhanced computed tomography parameters were validated with immunohistochemical assessments of tumor microvascular density (CD-31), tumor cell apoptosis (TUNEL), and proliferation (Ki-67). RESULTS: Regorafenib suppressed tumor vascularity (15.7±5.3 to 5.5±3.5%; p<0.05) and tumor perfusion (12.8±2.3 to 8.8±2.9 mL/100 mL/min; p = 0.063). Significantly lower microvascular density was observed in the therapy group (CD-31; 48±10 vs. 113±25, p<0.05). In regorafenib-treated tumors, significantly more apoptotic cells (TUNEL; 11844±2927 vs. 5097±3463, p<0.05) were observed. Dynamic contrast-enhanced computed tomography tumor perfusion and tumor vascularity correlated significantly (p<0.05) with microvascular density (CD-31; r = 0.84 and 0.66) and inversely with apoptosis (TUNEL; r = -0.66 and -0.71). CONCLUSIONS: Regorafenib significantly suppressed tumor vascularity (plasma volume) quantified by dynamic contrast-enhanced computed tomography in experimental colon carcinomas in rats with good-to-moderate correlations to an immunohistochemical gold standard. Tumor response biomarkers assessed by dynamic contrast-enhanced computed tomography may be a promising future approach to a more personalized and targeted cancer therapy.

European and Mexican vs US diagnostic extracts of Bermuda grass and cat in skin testing.

BACKGROUND: Laboratory testing of various diagnostic extracts has shown lower potencies for several European and Mexican extracts relative to the US Food and Drug Administration (FDA) reference (10,000 BAU/mL). Quantitative skin prick testing (QSPT) with Dermatophagoides pteronyssinus extracts have previously shown a similar picture. OBJECTIVE: To compare European and Mexican Bermuda grass (BG) and cat diagnostic extracts against an FDA-validated extract using QSPT. METHODS: Six diagnostic BG and cat extracts (1 reference FDA extract, 3 European extracts, 1 imported nonstandardized extract from the United States, and 1 Mexican extract) were tested with quadruplicate QSPT, as a concentrate and as 2 serial 2-fold dilutions, in cat and BG allergic individuals. RESULTS: BG showed good dose response in wheal size for the concentrate (1:2-1:4 dilutions; steep part of the curve). Cat showed poorer dose response. The Wilcoxon test for linked random samples was used to investigate whether the distribution of the reference differed from each of the test extracts to a statistically significant degree (2-sided asymptotic significance, α = .05). All BG and 2 cat extracts were statistically less potent than the 10,000 BAU/mL US reference. European BG extracts were 7,700, 4,100, and 1,600 BAU/mL, and cat extracts were 12,500, 4,400, and 5,100 BAU/mL. CONCLUSIONS: The potency of some diagnostic extracts of BG and cat used in Europe, Mexico, and the United States differs, with the US extracts being generally more potent. On the basis of provocation tests, optimal diagnostic concentrations should be determined. Similar comparisons using other manufacturers and therapeutic extracts might be interesting.

Skin prick test evaluation of Dermatophagoides pteronyssinus diagnostic extracts from Europe, Mexico, and the United States.

BACKGROUND: Previous Food and Drug Administration (FDA)-approved enzyme-linked immunosorbent assay testing of Dermatophagoides pteronyssinus diagnostic extracts showed potencies of 36% to 44% for 3 European extracts relative to the FDA standard (10,000 AU/mL). OBJECTIVE: To compare biological activity of various European D pteronyssinus diagnostic extracts against an FDA-validated extract using quantitative skin prick tests. METHODS: Six diagnostic D pteronyssinus extracts (1 reference extract, which was made up of 10,000 AU/mL of the FDA-approved extract; 3 European extracts; 1 US-Mexican extract, which is imported as raw material from the United States and sold in Mexico; and 1 Mexican extract) were tested during 2 skin prick test sessions as a concentrate and 2 serial 2-fold dilutions, in quadruplicate, on the backs of 19 patients with D pteronyssinus allergic rhinitis. The Wilcoxon test for linked random samples was used in each group to investigate whether the distribution of the reference extract differed from each of the test extracts to a statistically significant degree (test level alpha = .05). RESULTS: Extracts showed good dose response in wheal size for the concentrate compared with the 2 dilutions (steep part of the curve). All 3 European extracts (2-sided asymptotic significance, P = .003, P = .009, and P = .01, respectively) and 1 Mexican (P < .001) extract were less potent than the reference extract. European extracts varied in potency from 5,400 to 6,126 AU/mL, the US-Mexican extract had a potency of 7,444 AU/mL, and the Mexican extract had a potency of 2,099 AU/mL. CONCLUSIONS: Our study confirmed the results from previous in vitro testing. Various diagnostic extracts of D pteronyssinus used in Europe and Mexico are less potent than those used in the United States. Similar comparisons using therapeutic extracts would be of interest.

Role of intermittent hypoxia in the treatment of bronchial asthma and chronic obstructive pulmonary disease.

PURPOSE OF REVIEW: The purpose of this review is to describe the impact that exposure to intermittent hypoxic training (IHT) could have on bronchial asthma and chronic obstructive pulmonary disease (COPD). This is of particular interest, as an increasing number of patients suffer from severe symptoms of bronchial asthma and COPD and desire more effective and efficient treatment options with fewer side effects. RECENT FINDINGS: Exposure to IHT has been shown to raise baroreflex sensitivity to normal levels and to selectively increase hypercapnic ventilatory response, total exercise time, total haemoglobin mass, and lung diffusion capacity for carbon monoxide in COPD patients. However, evidence proving that IHT leads to health benefit effects in bronchial asthma patients has not been produced by recent literature. SUMMARY: Recent research outlines the value of IHT as a therapeutic strategy for the treatment of COPD patients, leading to more efficient ventilation. Additionally, IHT might represent an attractive method to complement the known beneficial effects of exercise training and to rebalance early autonomic dysfunction in COPD patients. Future research examining the potential risks and benefits of IHT could pave the way for the development of new therapeutic approaches for patients suffering from bronchial asthma and COPD.