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Dietary fats, olive oil and respiratory diseases in Italian adults: A population-based study.
Cazzoletti, L, Zanolin, ME, Spelta, F, Bono, R, Chamitava, L, Cerveri, I, Garcia-Larsen, V, Grosso, A, Mattioli, V, Pirina, P, et al
Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology. 2019;(6):799-807
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Abstract
BACKGROUND Fat intake has been associated with respiratory diseases, with conflicting results. OBJECTIVE We studied the association between asthma and rhinitis with dietary fats, and their food sources in an Italian population. METHODS Clinical and nutritional information was collected for 871 subjects (aged 20-84) from the population-based multi-case-control study Genes Environment Interaction in Respiratory Diseases (GEIRD): 145 with current asthma (CA), 77 with past asthma (PA), 305 with rhinitis and 344 controls. Food intake was collected using the EPIC (European Investigation into Cancer and Nutrition) Food Frequency Questionnaire. The associations between fats and respiratory diseases were estimated by multinomial models. Fats and their dietary sources were analysed both as continuous variables and as quartiles. RESULTS Monounsaturated fatty acids and oleic acid were associated with a reduced risk of CA in both continuous (RRR = 0.68, 95%CI: 0.48; 0.96; RRR = 0.69; 95%CI: 0.49; 0.97, per 10 g, respectively) and per-quartile analyses (p for trend = 0.028 and 0.024, respectively). Olive oil was associated with a decreased risk of CA (RRR = 0.80; 95%CI: 0.65; 0.98 per 10 g). An increased risk of rhinitis was associated with moderate total fat and SFA intake. CONCLUSIONS High dietary intakes of oleic acid and of olive oil are associated with a lower risk of asthma but not of rhinitis.
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Carotenoids, fatty acids and disease burden in obese minority adolescents with asthma.
Tobias, TAM, Wood, LG, Rastogi, D
Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology. 2019;(6):838-846
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BACKGROUND Paediatric obesity-related asthma causes high disease burden, is associated with metabolic abnormalities, has few therapeutic options, and disproportionately affects urban minority children. Although poor diet quality is linked to asthma, the association of nutritional status with disease burden among children with obesity-related asthma is not well understood. OBJECTIVE To quantify nutritional status, defined as concentrations of serum carotenoids and n-3 fatty acids, and its association with pulmonary function and metabolic markers among obese asthmatic children. METHODS We quantified serum carotenoids and fatty acids in a study cohort of 158 urban minority adolescents including 39 obese asthmatics, 39 healthy weight asthmatics, 38 obese controls and 42 healthy weight controls and compared between the groups. We correlated carotenoid and fatty acid levels with pulmonary function indices and with insulin resistance and dyslipidemia. RESULTS Mean total carotenoids were lowest in obese asthmatic children (0.41 μg/mL), lower than healthy weight asthmatics (0.52 μg/mL, P < 0.05) and healthy weight controls (0.60 μg/mL, P < 0.001). n-6/n-3 polyunsaturated fatty acid (PUFA) ratio also differed between the groups (P < 0.05). Total carotenoids positively correlated with per cent-predicted FEV1 and inversely correlated with insulin resistance among obese asthmatics only. n-6/n-3 PUFA ratio inversely correlated with per cent-predicted FEV1 in obese asthmatics. CONCLUSIONS & CLINICAL RELEVANCE Our findings suggest that carotenoids, which are lowest in obese asthmatic children, may have protective effects on metabolic health and pulmonary function among obese asthmatic children. Similarly, n-3 PUFA appear to be protective for pulmonary function.
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Maternal and neonatal 25-hydroxyvitamin D concentrations and school-age lung function, asthma and allergy. The Generation R Study.
Mensink-Bout, SM, van Meel, ER, de Jongste, JC, Voortman, T, Reiss, IK, De Jong, NW, Jaddoe, VWV, Duijts, L
Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology. 2019;(6):900-910
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BACKGROUND Vitamin D deficiency in early life might affect the developing lung and immune system, and subsequently influence the risk of asthma and allergy in later life. OBJECTIVE We examined the associations of 25-hydroxyvitamin D concentrations in mid-gestation and at birth with lung function, asthma, inhalant allergic sensitization and inhalant allergy at school-age. METHODS This study among 4951 children and their mothers was embedded in a population-based prospective cohort in Rotterdam, the Netherlands. Maternal venous blood samples in mid-gestation and umbilical cord blood samples at birth were used to determine 25-hydroxyvitamin D concentrations. At age 10 years, lung function was measured by spirometry, current asthma and physician-diagnosed inhalant allergy by questionnaire, and inhalant allergic sensitization by skin prick tests. We used multivariable regression models to examine associations. RESULTS Higher 25-hydroxyvitamin D concentrations in mid-gestation were associated with a higher forced vital capacity (FVC), but a lower forced expiratory volume in 1 second/FVC (FEV1 /FVC) and a lower forced expiratory flow after exhaling 75% of FVC (FEF75 ) (Z-score differences [95% CI] 0.02 [0.00, 0.03], -0.02 [-0.03, -0.01] and -0.01 [-0.03, -0.00], respectively, per 10 nmol/L 25-hydroxyvitamin D), but not with asthma. Furthermore, higher 25-hydroxyvitamin D concentrations in mid-gestation were associated with an increased risk of inhalant allergy (Odds Ratio [95% CI] 1.07 [1.02, 1.12]), but not with inhalant allergic sensitization. After additional adjustment for child's 25-hydroxyvitamin D concentrations at the age of 6 years, only the associations of 25-hydroxyvitamin D concentrations in mid-gestation with FEV1 /FVC and FEF75 remained. We did not find consistent associations of 25-hydroxyvitamin D concentrations at birth with respiratory or allergy outcomes. CONCLUSION AND CLINICAL RELEVANCE Our results suggest that maternal 25-hydroxyvitamin D concentrations in mid-gestation may influence lung development. The clinical implications of the observed associations remain unclear.
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Tiotropium add-on therapy is safe and reduces seasonal worsening in paediatric asthma patients.
Vogelberg, C, Szefler, SJ, Vrijlandt, EJLE, Boner, AL, Engel, M, El Azzi, G, Vulcu, SD, Moroni-Zentgraf, PM, Eickmeier, O, Hamelmann, EH
The European respiratory journal. 2019;(6)
Abstract
There remains an unmet need for effective, well-tolerated therapeutic options in paediatric patients with not fully controlled asthma, for whom safety is of paramount importance.Data were pooled from five randomised, double-blind, placebo-controlled studies evaluating tiotropium 5 or 2.5 µg versus placebo add-on therapy in patients with symptomatic asthma aged 1-17 years. Analysis included adverse events (AEs) and serious AEs (SAEs) reported throughout and for 30 days following treatment.Of 1691 patients treated, 1119 received tiotropium. Reporting of AEs was low and comparable across all groups: tiotropium 5 µg (51%), tiotropium 2.5 µg (51%) and placebo (54%). Reporting of drug-related AEs, those leading to discontinuation and SAEs was also low and balanced between treatment groups, irrespective of age, disease severity or sex. The number of AEs related to asthma symptoms and exacerbations was lower with tiotropium (5 µg) than with placebo, particularly during the seasonal peaks of these AEs.This comprehensive analysis of a large safety database allowed subgroup analyses that are often impractical with individual trials and provides further support for the safety of once-daily tiotropium Respimat add-on therapy in paediatric patients with symptomatic asthma.
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Evaluation of Bioequivalence Between the New Procaterol Hydrochloride Hydrate Dry Powder Inhaler and the Approved Dry Powder Inhaler in Patients With Asthma in a Randomized, Double-Blind, Double-Dummy, Crossover Comparison Study: A Phase 3 Study.
Shirai, R, Suzaki, Y, Sato, K, Takeuchi, Y, Tokimatsu, I, Koga, N, Kadota, J, Ohashi, K
Clinical pharmacology in drug development. 2018;(4):392-399
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Procaterol hydrochloride hydrate (procaterol) is a β2 -adrenergic receptor agonist that induces a strong bronchodilatory effect. The procaterol dry powder inhaler (DPI) has been frequently used in patients with bronchial asthma or chronic obstructive pulmonary disease. We evaluated the bioequivalence and safety between the new procaterol DPI (new DPI) and the approved procaterol DPI (approved DPI). This study was a randomized, double-blind, double-dummy, crossover comparison to evaluate the pharmacodynamic equivalence of the new DPI and the approved DPI in patients with bronchial asthma. Primary efficacy variables were area under the concentration-time curve (AUC) forced expiratory volume in the first second (FEV1 )/h and maximum FEV1 during the 480-minute measurement period. Patients were divided into 2 groups, New-DPI-First (n = 8) and Approved-DPI-First (n = 8), according to the investigational medical product that was administered first. Patients inhaled 20 μg of procaterol in each period. FEV1 was measured by a spirometer at predose and at 15, 30, 60, 90, 120, 180, 240, 360, and 480 minutes after each investigational medical product administration. Equivalence was evaluated by confirming that the 2-sided 90%CIs for the difference between the new and the approved DPI in means of AUC (FEV1 )/h and maximum FEV1 were within the acceptance criteria of -0.15 to 0.15 L. The difference in means of AUC (FEV1 )/h and maximum FEV1 was 0.041 L and 0.033 L, respectively, and the 90%CI was 0.004 to 0.078 L and -0.008 to 0.074 L, respectively. These CIs were both within the acceptance criteria. The new DPI was assessed as being bioequivalent to the approved DPI.
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A Randomized, Multicenter, Double-blind, Phase III Study to Evaluate the Efficacy on Allergic Rhinitis and Safety of a Combination Therapy of Montelukast and Levocetirizine in Patients With Asthma and Allergic Rhinitis.
Kim, MK, Lee, SY, Park, HS, Yoon, HJ, Kim, SH, Cho, YJ, Yoo, KH, Lee, SK, Kim, HK, Park, JW, et al
Clinical therapeutics. 2018;(7):1096-1107.e1
Abstract
PURPOSE The aim of this study was to evaluate the efficacy and safety of a fixed-dose combination of montelukast and levocetirizine in patients with perennial allergic rhinitis with mild to moderate asthma compared with the efficacy and safety of montelukast alone. METHODS This study was a 4-week, randomized, multicenter, double-blind, Phase III trial. After a 1-week placebo run-in period, the subjects were randomized to receive montelukast (10 mg/day, n = 112) or montelukast (10 mg/day)/levocetirizine (5 mg/day) (n = 116) treatment for 4 weeks. The primary efficacy end point was mean daytime nasal symptom score. Other efficacy end points included mean nighttime nasal symptom score, mean composite symptom score, overall assessment of allergic rhinitis by both subjects and physicians, forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), FEV1/FVC, asthma control test score, and the frequency of rescue medication used during the treatment period. FINDINGS Of 333 patients screened for this study, 228 eligible patients were randomized to treatment. The mean (SD) age of patients was 43.32 (15.02) years, and two thirds of subjects were female (66.67%). The demographic characteristics were similar between the treatment groups. Compared with the montelukast group, the montelukast/levocetirizine group reported significant reductions in mean daytime nasal symptom score (least squares mean [SE] of combination vs montelukast, -0.98 [0.06] vs -0.81 [0.06]; P = 0.045). For all other allergic rhinitis efficacy end points, the montelukast/levocetirizine group showed greater improvement than the montelukast group. Similar results were observed in overall assessment scores and in FEV1, FVC, FEV1/FVC, and asthma control test score changes from baseline for the 2 treatment groups. Montelukast/levocetirizine was well tolerated, and the safety profile was similar to that observed in the montelukast group. IMPLICATIONS The fixed-dose combination of montelukast and levocetirizine was effective and safe in treating perennial allergic rhinitis in patients with asthma compared with montelukast alone. ClinicalTrials.gov identifier: NCT02552667.
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Effects of benralizumab on airway eosinophils in asthmatic patients with sputum eosinophilia.
Laviolette, M, Gossage, DL, Gauvreau, G, Leigh, R, Olivenstein, R, Katial, R, Busse, WW, Wenzel, S, Wu, Y, Datta, V, et al
The Journal of allergy and clinical immunology. 2013;(5):1086-1096.e5
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Abstract
BACKGROUND Many asthmatic patients exhibit sputum eosinophilia associated with exacerbations. Benralizumab targets eosinophils by binding IL-5 receptor α, inducing apoptosis through antibody-dependent cell-mediated cytotoxicity. OBJECTIVES We sought to evaluate the safety of benralizumab in adults with eosinophilic asthma and its effects on eosinophil counts in airway mucosal/submucosal biopsy specimens, sputum, bone marrow, and peripheral blood. METHODS In this multicenter, double-blind, placebo-controlled phase I study, 13 subjects were randomized to single-dose intravenous placebo or 1 mg/kg benralizumab (day 0; cohort 1), and 14 subjects were randomized to 3 monthly subcutaneous doses of placebo or 100 or 200 mg of benralizumab (days 0, 28, and 56; cohort 2). Cohorts 1 and 2 were consecutive. RESULTS The incidence of adverse events was similar between groups. No serious adverse events related to benralizumab occurred. In cohort 1 intravenous benralizumab produced a median decrease from baseline of 61.9% in airway mucosal eosinophil counts (day 28; placebo: +19.6%; P = .28), as well as an 18.7% decrease (day 21) in sputum and a 100% decrease (day 28) in blood counts. Eosinophils were not detectable in bone marrow of benralizumab-treated subjects (day 28, n = 4). In cohort 2 subcutaneous benralizumab demonstrated a combined (100 + 200 mg) median reduction of 95.8% in airway eosinophil counts (day 84; placebo, 46.7%; P = .06), as well as an 89.9% decrease (day 28) in sputum and a 100% decrease (day 84) in blood counts. CONCLUSION Single-dose intravenous and multiple-dose subcutaneous benralizumab reduced eosinophil counts in airway mucosa/submucosa and sputum and suppressed eosinophil counts in bone marrow and peripheral blood. The safety profile supports further development. Additional studies are needed to assess the clinical benefit in asthmatic patients.
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Genome-wide association analysis of circulating vitamin D levels in children with asthma.
Lasky-Su, J, Lange, N, Brehm, JM, Damask, A, Soto-Quiros, M, Avila, L, Celedón, JC, Canino, G, Cloutier, MM, Hollis, BW, et al
Human genetics. 2012;(9):1495-505
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Abstract
Vitamin D deficiency is becoming more apparent in many populations. Genetic factors may play a role in the maintenance of vitamin D levels. The objective of this study was to perform a genome-wide analysis (GWAS) of vitamin D levels, including replication of prior GWAS results. We measured 25-hydroxyvitamin D (25(OH)D) levels in serum collected at the time of enrollment and at year 4 in 572 Caucasian children with asthma, who were part of a multi-center clinical trial, the Childhood Asthma Management Program. Replication was performed in a second cohort of 592 asthmatics from Costa Rica and a third cohort of 516 Puerto Rican asthmatics. In addition, we attempted replication of three SNPs that were previously identified in a large GWAS of Caucasian individuals. The setting included data from a clinical trial of childhood asthmatics and two cohorts of asthmatics recruited for genetic studies of asthma. The main outcome measure was circulating 25(OH)D levels. The 25(OH)D levels at the two time-points were only modestly correlated with each other (intraclass correlation coefficient = 0.33) in the CAMP population. We identified SNPs that were nominally associated with 25(OH)D levels at two time-points in CAMP, and replicated four SNPs in the Costa Rican cohort: rs11002969, rs163221, rs1678849, and rs4864976. However, these SNPs were not significantly associated with 25(OH)D levels in a third population of Puerto Rican asthmatics. We were able to replicate the SNP with the strongest effect, previously reported in a large GWAS rs2282679 (GC), and we were able to replicate another SNP, rs10741657 (CYP2R1), to a lesser degree. We were able to replicate two of three prior significant findings in a GWAS of 25(OH)D levels. Other SNPs may be additionally associated with 25(OH)D levels in certain populations.
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Association of dietary soy genistein intake with lung function and asthma control: a post-hoc analysis of patients enrolled in a prospective multicentre clinical trial.
Bime, C, Wei, CY, Holbrook, J, Smith, LJ, Wise, RA
Primary care respiratory journal : journal of the General Practice Airways Group. 2012;(4):398-404
Abstract
BACKGROUND Broad dietary patterns have been linked to asthma but the relative contribution of specific nutrients is unclear. Soy genistein has important anti-inflammatory and other biological effects that might be beneficial in asthma. A positive association was previously reported between soy genistein intake and lung function but not with asthma exacerbations. AIMS To conduct a post-hoc analysis of patients with inadequately controlled asthma enrolled in a prospective multicentre clinical trial to replicate this association. METHODS A total of 300 study participants were included in the analysis. Dietary soy genistein intake was measured using the Block Soy Foods Screener. The level of soy genistein intake (little or no intake, moderate intake, or high intake) was compared with baseline lung function (pre-bronchodilator forced expiratory volume in 1 second (FEV(1))) and asthma control (proportion of participants with an episode of poor asthma control (EPAC) and annualised rates of EPACs over a 6-month follow-up period. RESULTS Participants with little or no genistein intake had a lower baseline FEV(1) than those with a moderate or high intake (2.26 L vs. 2.53 L and 2.47 L, respectively; p=0.01). EPACs were more common among those with no genistein intake than in those with a moderate or high intake (54% vs. 35% vs. 40%, respectively; p<0.001). These findings remained significant after adjustment for patient demographics and body mass index. CONCLUSIONS In patients with asthma, consumption of a diet with moderate to high amounts of soy genistein is associated with better lung function and better asthma control.
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Admissions to Canadian hospitals for acute asthma: a prospective, multicentre study.
Rowe, BH, Villa-Roel, C, Abu-Laban, RB, Stenstrom, R, Mackey, D, Stiell, IG, Campbell, S, Young, B
Canadian respiratory journal. 2010;(1):25-30
Abstract
BACKGROUND Asthma exacerbations constitute one of the most common causes of emergency department (ED) attendance in most developed countries. While severe asthma often requires hospitalization, variability in admission practices has been observed. OBJECTIVE To describe the factors associated with admission to Canadian hospitals for acute asthma after ED treatment. METHODS Subjects 18 to 55 years of age treated for acute asthma in 20 Canadian EDs prospectively underwent a structured ED interview (n=695) and telephone interview two weeks later. RESULTS The median age of the patients was 30 years, and the majority were women (62.8%). The admission rate was 13.1% (95% CI 10.7% to 15.8%). Admitted patients were older, more often receiving oral or inhaled corticosteroids at presentation, and more frequently receiving systemic corticosteroids and magnesium sulphate in the ED. Similar proportions received beta-2 agonists and/or ipratropium bromide within 1 h of arrival. On multivariable analyses, factors associated with admission included age, previous admission in the past two years, more than eight beta-2 agonist puffs in the past 24 h, a Canadian Triage and Acuity Score of 1 to 2, a respiratory rate of greater than 22 breaths/min and an oxygen saturation of less than 95%. CONCLUSION The admission rate for acute asthma from these Canadian EDs was lower than reported in other North American studies. The present study provides insight into practical factors associated with admission for acute asthma and highlights the importance of history and asthma severity markers on ED decision making. Further efforts to standardize ED management and expedite admission decision-making appear warranted.