Carlos A. Camargo

Body Mass Index and Response to Asthma Therapy: Fluticasone Propionate/Salmeterol versus Montelukast

We studied the relationship between body mass index (BMI) on responses to asthma therapy using a retrospective analysis of four previously reported clinical trials. Fluticasone propionate (FP)/salmeterol via Diskus 100/50 μg twice daily and montelukast (MON) 10 mg daily were compared. BMI was classified as underweight (less than 20 kg/m2), normal (20–24.9 kg/m2), overweight (25–29.9 kg/m2), obese-1 (30–34.9 kg/m2), obese-2 (35–39.9 kg/m2), or obese-3 (at least 40 kg/m2). Outcomes assessed included forced expiratory volume in one second (FEV1), asthma symptom score, and albuterol use. FP/salmeterol produced greater improvements compared to MON in each of the asthma outcomes studied over the entire BMI range at the week-12 endpoint, with statistically significant differences noted among normal, overweight, obese-1, and obese-3 subjects. The within-treatment responses to FP/salmeterol across BMI ranges at the week-12 endpoint was statistically significantly greater in normal compared to obese-3 for FEV1 and albuterol use, and in overweight compared to the obese-3 for each outcome studied. The within-treatment comparisons of MON across BMI ranges were significant for albuterol use in normal and underweight compared to obese-3 at the week-12 endpoint. Compared to subjects with normal BMI, the onset to peak FEV1 may require longer treatment exposure in the very obese. Treatment responses to FP/salmeterol were consistently greater compared to MON and persisted at higher BMI.

Vitamin D Status and Periodontal Disease Among Pregnant Women

BACKGROUND Maternal periodontal disease is found in < or = 40% of pregnant women and is associated with adverse pregnancy outcomes. Vitamin D deficiency may play a role in periodontal disease and tooth loss, and insufficient vitamin D status is common among pregnant women. The objective of this study is to examine the relationship between maternal vitamin D status and periodontal disease. METHODS A case-control study was conducted. Cases were defined as pregnant women with clinical moderate to severe periodontal disease; controls were pregnant women who were periodontally healthy. Maternal data were chart abstracted and serum was collected between 14 and 26 weeks of gestation. Serum 25-hydroxyvitamin D (25[OH]D) levels were measured using liquid chromatography-tandem mass spectrometry. Median serum 25(OH)D levels and prevalence of vitamin D insufficiency (defined as <75 nmol/l) were compared between cases and controls. The odds ratio and 95% confidence interval for moderate to severe periodontal disease among women with vitamin D insufficiency was calculated using multivariable logistic regression, adjusting for maternal race, season of blood draw, and other potential confounders. RESULTS A total of 117 cases were compared to 118 controls. Cases had lower median 25(OH)D levels than controls (59 versus 100 nmol/l; P <0.001) and were more likely to have vitamin D insufficiency (65% versus 29%; P <0.001). The adjusted odds ratio (95% confidence interval) for moderate to severe periodontal disease among women with vitamin D insufficiency was 2.1 (0.99 to 4.5). CONCLUSIONS Vitamin D insufficiency (serum 25[OH]D <75 nmol/l) is associated with maternal periodontal disease during pregnancy. Vitamin D supplementation represents a potential therapeutic strategy to improve maternal oral health.

The Vitamin D Assessment (ViDA) Study: design of a randomized controlled trial of vitamin D supplementation for the prevention of cardiovascular disease, acute respiratory infection, falls and non-vertebral fractures

Observational studies have shown that low vitamin D status is associated with an increased risk of cardiovascular disease, acute respiratory infection, falls and non-vertebral fractures. We recruited 5110 Auckland adults, aged 50-84 years, into a randomized, double-blind, placebo-controlled trial to test whether vitamin D supplementation protects against these four major outcomes. The intervention is a monthly cholecalciferol dose of 100,000IU (2.5mg) for an estimated median 3.3 years (range 2.5-4.2) during 2011-2015. Participants were recruited primarily from family practices, plus community groups with a high proportion of Maori, Pacific, or South Asian individuals. The baseline evaluation included medical history, lifestyle, physical measurements (e.g. blood pressure, arterial waveform, lung function, muscle function), and a blood sample (stored at -80°C for later testing). Capsules are being mailed to home addresses with a questionnaire to collect data on non-hospitalized outcomes and to monitor adherence and potential adverse effects. Other data sources include New Zealand Ministry of Health data on mortality, hospitalization, cancer registrations and dispensed pharmaceuticals. A random sample of 438 participants returned for annual collection of blood samples to monitor adherence and safety (hypercalcemia), including repeat physical measurements at 12 months follow-up. The trial will allow testing of a priori hypotheses on several other endpoints including: weight, blood pressure, arterial waveform parameters, heart rate variability, lung function, muscle strength, gait and balance, mood, psoriasis, bone density, and chronic pain.

Mortality after an emergency department visit for exacerbation of chronic obstructive pulmonary disease

Objective. To describe the mortality after emergency department (ED) visits for chronic obstructive pulmonary disease (COPD) exacerbation. Design. Retrospective cohort study of ED patients with COPD exacerbation. Setting. Administrative data analysis. Participants. Patients age 55 and over who visited the ED during a 2-year period with primary ICD-9 codes of 491, 492, or 496. Measurements. Demographic characteristics, comorbid conditions, hospital utilization for COPD, and vital status. Results. During the study period, there were 482 index visits with a median follow-up of 1,1 28 days (3.1 years). Demographic characteristics of the cohort were as follows: mean age 72 years, 56% female, 93% White, and 37% currently married. Mortality increased over time: 5% at 30 days, 9% at 60 days, 11% at 90 days, 16% at 180 days, 23% at 1 year, 32% at 2 years, and 39% at 3 years. At the end of follow-up, 220 (46%) patients had died. On multivariate analysis, independent predictors of mortality were increasing age (hazard ratio [HR] 1.3 per 5-year increase, 95% CI 1.2–1.4), having congestive heart failure (HR 1.6, 95% CI 1.2–2.1), having metastatic solid tumor (HR 3.3, 95% CI 2.0–5.5), and hospital utilization for COPD exacerbation during past year (HR 1.9, 95% CI 1.4–2.6). Conclusion. The mortality rate after an ED visit for COPD exacerbation is quite high. Mortality is related to older age, specific comorbid conditions, and history of prior COPD exacerbations.

Circadian-rhythm differences among emergency department patients with chronic obstructive pulmonary disease exacerbation.

The purpose of the study was determine whether patients with chronic obstructive pulmonary disease (COPD) exacerbation who present to the emergency department (ED) during the night (00:00 to 07:59 h) vs. other times of the day have more severe COPD exacerbation, require more intensive treatment, and have worse clinical outcomes. A multicenter cohort study was completed involving 29 EDs in the United States and Canada. Using a standard protocol, consecutive ED patients with COPD exacerbation were interviewed, and their charts were reviewed. Of 582 patients enrolled, 52% were women, and the median age was 71 yrs (interquartile range, 64–77 yrs). Nighttime patients (15% of cohort) did not differ from patients presenting at other times except that they were less likely to have private insurance, more likely to have a history of corticosteroid use, and have a shorter duration of symptoms exacerbation. Except for a few features indicative of more severe COPD exacerbation (such as higher respiratory rate at ED presentation, greater likelihood of receiving noninvasive positive pressure ventilation, and increased risk of endotracheal intubation), nighttime patients did not differ from other patients with respect to ED management. Nighttime patients were approximately three‐fold more likely to be intubated in the ED (odds ratio, 3.46; 95% confidence interval, 1.10–10.9). There were no day‐night differences regarding ED disposition and post‐ED relapse. Except for some features indicating more severe exacerbation, nighttime ED patients had similar chronic COPD characteristics, received similar treatments in the ED, and had similar clinical outcomes compared with patients presenting to the ED at other times of the day.

Efficacy and Safety of Benralizumab, a Monoclonal Antibody against IL-5Rα, in Uncontrolled Eosinophilic Asthma

Nonresponders to maximal guideline-based therapies of asthma account for most of the morbidity, mortality, and economic burden of the disease. Because eosinophils are key effector cells in asthmatic airway inflammation, blocking IL-5, the main cytokine responsible for its survival and activation, seems to be a rational strategy. While previous monoclonal antibodies against the IL-5 ligand resulted in inconsistent improvements in asthma outcomes, benralizumab has shown promise. Benralizumab is a monoclonal antibody against IL-5 receptor, and has an enhanced antibody dependent cell-mediated cytotoxicity function. In this article, we review the theoretical advantages of benralizumab compared to previous compounds, as well as current status of the clinical development of benralizumab in asthma. Lastly, we briefly discuss the potential role of benralizumab in chronic obstructive pulmonary disease.

Acute exacerbations of COPD: delay in presentation and the risk of hospitalization.

To determine if a delay in presentation to the emergency department (ED) after the onset of symptoms of an acute exacerbation of chronic obstructive pulmonary disease (AECOPD) increases the risk of hospital admission. A prospective cohort study utilizing data from 396 patient visits to 29 North American EDs. Inclusion criteria were age ≥ 55 years; a diagnosis of COPD; and presentation for treatment of AECOPD, as defined by increasing shortness of breath, worsening cough, or change in sputum production at presentation. The median age was 69 years and 54% were female. Most patients (70%) presented to the ED > 24 hours after symptom onset, and most (61%) were hospitalized. On multivariate logistic regression analysis, after adjusting for 12 potential confounders (including demographics, clinical features, other diagnoses, and bronchodilator use before arrival), a delay in presentation ≥ 24 hours was associated with a over two-fold increase in the odds of admission (odds ratio = 2.2, 95% confidence interval 1.1–4.8). This increase in risk persisted for delay in presentation ≥ 12 hours in place of 24 hours, after restricting the analysis to patients admitted outside the intensive care unit, and to those reporting the ED as their usual site of care. A majority of patients delay presentation to the ED for ≥ 24 hours after symptom onset, and are at higher risk of hospitalization. Early presentation should be emphasized to patients and caregivers to advance efforts to decrease the morbidity, mortality, and costs of AECOPD treatment.

Vitamin D status, aeroallergen sensitization, and allergic rhinitis: A systematic review and meta-analysis

ABSTRACT Purpose: The role of vitamin D status in the etiology of allergic diseases is uncertain. The aim of this study was to investigate the association of vitamin D status with risk of two main outcomes: aeroallergen sensitization and allergic rhinitis (AR). Methods: We performed a systematic review of Medline, Scopus, Science Citation Index, and Google Scholar databases. Studies were included if they reported on prevalent or incident cases of aeroallergen sensitization or AR according to vitamin D status. Quality assessment, data extraction and meta-analysis were performed. Results: A total of 21 observational studies were included. Children with serum 25(OH)D ≥75 nmol/L had significantly reduced odds of aeroallergen sensitization, but neither vitamin D intake in pregnancy nor vitamin D supplementation in infancy were associated with risk of AR. Individuals with serum 25(OH)D ≥75 nmol/L had lower prevalence of AR compared to those with serum 25(OH)D <50 nmol/L (OR; 0.71, 95%CI; (0.56-0.89), p = 0.04). This association was mainly observed in adult men; prevalence of AR was lower in men with serum 25(OH)D ≥75 nmol/L compared to men with serum 25(OH)D <50 nmol/L, while this association was not observed in women. Conclusions: The current literature suggests significant age- and sex-specific relations of vitamin D status to risk of aeroallergen sensitization and AR.

Advancing our understanding of infant bronchiolitis through phenotyping and endotyping: clinical and molecular approaches

ABSTRACT Introduction: Bronchiolitis is a major public health problem worldwide. However, no effective treatment strategies are available, other than supportive care. Areas covered: Although bronchiolitis has been considered a single disease diagnosed based on clinical characteristics, emerging evidence supports both clinical and pathobiological heterogeneity. The characterization of this heterogeneity supports the concept that bronchiolitis consists of multiple phenotypes or consistent grouping of characteristics. Expert commentary: Using unbiased statistical approaches, multidimentional clinical characteristics will derive bronchiolitis phenotypes. Furthermore, molecular and systems biology approaches will, by linking pathobiology to phenotype, identify endotypes. Large cohort studies of bronchiolitis with comprehensive clinical characterization and system-wide profiling of the ‘-omics’ data (e.g., host genome, transcriptome, epigenome, viral genome, microbiome, metabolome) should enhance our ability to molecularly understand these phenotypes and lead to more targeted and personalized approaches to bronchiolitis treatment.

Vitamin D, Childhood Wheezing, Asthma, and Chronic Obstructive Pulmonary Disease

Publisher Summary This chapter examines the relation of vitamin D to childhood wheezing and asthma, along with emerging evidence on the role of vitamin D among patients with chronic obstructive pulmonary disease. Vitamin D deficiency appears to increase risk of acute respiratory infections, which cause incident childhood wheezing and asthma exacerbations. Few studies have also suggested that vitamin D deficiency affects risk of incident asthma. Research studies have also indicated that Vitamin D may contribute to human lung development. Vitamin Ds myriad effects on innate and adaptive immunity provide biological plausibility for how vitamin D deficiency—increases risk of infection, lowers therapeutic response to corticosteroids, and increases risk of other atopic conditions, such as eczema and food allergy. However, the role of vitamin D in the etiology of chronic obstructive pulmonary disease (COPD) and its exacerbations remain uncertain. Further studies, especially randomized controlled trials (RCTs), are needed to better establish the effects of vitamin D on acute respiratory infections and other respiratory disorders, particularly in fall or winter at higher latitudes.