Asthma exacerbations are associated with a decline in lung function: a longitudinal population-based study.

RATIONALE: Progressive lung function (LF) decline in patients with asthma contributes to worse outcomes. Asthma exacerbations are thought to contribute to this decline; however, evidence is limited with mixed results. METHODS: This historical cohort study of a broad asthma patient population in the Optimum Patient Care Research Database, examined asthma patients with 3+eligible post-18th birthday peak expiratory flow rate (PEF) records (primary analysis) or records of forced expiratory flow in 1 s (FEV1) (sensitivity analysis). Adjusted linear growth models tested the association between mean annual exacerbation rate (AER) and LF trajectory. RESULTS: We studied 1 09 182 patients with follow-up ranging from 5 to 50 years, of which 75 280 had data for all variables included in the adjusted analyses. For each additional exacerbation, an estimated additional -1.34 L/min PEF per year (95% CI -1.23 to -1.50) were lost. Patients with AERs >2/year and aged 18-24 years at baseline lost an additional -5.95 L/min PEF/year (95% CI -8.63 to -3.28) compared with those with AER 0. These differences in the rate of LF decline between AER groups became progressively smaller as age at baseline increased. The results using FEV1 were consistent with the above. CONCLUSION: To our knowledge, this study is the largest nationwide cohort of its kind and demonstrates that asthma exacerbations are associated with faster LF decline. This was more prominent in younger patients but was evident in older patients when it was related to lower starting LF, suggesting a persistent deteriorating phenotype that develops in adulthood over time. Earlier intervention with appropriate management in younger patients with asthma could be of value to prevent excessive LF decline.

International severe asthma registry (ISAR): protocol for a global registry.

BACKGROUND: Severe asthma exerts a disproportionately heavy burden on patients and health care. Due to the heterogeneity of the severe asthma population, many patients need to be evaluated to understand the clinical features and outcomes of severe asthma in order to facilitate personalised and targeted care. The International Severe Asthma Registry (ISAR) is a multi-country registry project initiated to aid in this endeavour. METHODS: ISAR is a multi-disciplinary initiative benefitting from the combined experience of the ISAR Steering Committee (ISC; comprising 47 clinicians and researchers across 29 countries, who have a special interest and/or experience in severe asthma management or establishment and maintenance of severe asthma registries) in collaboration with scientists and experts in database management and communication. Patients (≥18 years old) receiving treatment according to the 2018 definitions of the Global Initiative for Asthma (GINA) Step 5 or uncontrolled on GINA Step 4 treatment will be included. Data will be collected on a core set of 95 variables identified using the Delphi method. Participating registries will agree to provide access to and share standardised anonymous patient-level data with ISAR. ISAR is a registered data source on the European Network of Centres for Pharmacoepidemiology and Pharmacovigilance. ISAR's collaborators include Optimum Patient Care, the Respiratory Effectiveness Group (REG) and AstraZeneca. ISAR is overseen by the ISC, REG, the Anonymised Data Ethics & Protocol Transparency Committee and the ISAR operational committee, ensuring the conduct of ethical, clinically relevant research that brings value to all key stakeholders. CONCLUSIONS: ISAR aims to offer a rich source of real-life data for scientific research to understand and improve disease burden, treatment patterns and patient outcomes in severe asthma. Furthermore, the registry will provide an international platform for research collaboration in respiratory medicine, with the overarching aim of improving primary and secondary care of adults with severe asthma globally.

Whole milk consumption and risk of cardiovascular disease and mortality: Isfahan Cohort Study.

BACKGROUND: The association between milk intake and cardiovascular disease (CVD) and mortality risk is still controversial but data from Middle-Eastern populations are scarce. We aimed to study these associations in an Iranian population. METHODS: We used the Isfahan Cohort Study, a population-based prospective study of 6504 adult Iranians. In this analysis, we included 5432 participants free of CVD at baseline with at least one follow-up. Data on whole milk intake and other dietary factors were collected by a food frequency questionnaire at baseline. Cox proportional hazard regression was used to predict risk of CVD events, comprising coronary heart disease (CHD) and stroke, and mortality according to frequency of whole milk intake with adjustment for other potential confounders. RESULTS: During a median 10.9 years of follow-up, we documented 705 new cases of CVD comprising 564 CHD and 141 stroke cases. Compared with non-consumers, less than daily intake of whole milk was significantly associated with lower risk of CVD (HR 0.80, 95% CI 0.65-0.97), CHD (HR 0.81, 95% CI 0.65-0.99), and a non-significant lower risk of stroke (HR 0.79, 95% CI 0.50-1.27). Daily intake of whole milk was not significantly associated with CVD (HR 1.25, 95% CI 0.89-1.75), CHD, and stroke, but was associated with higher risk of all-cause mortality (HR 1.54, 95% CI 1.04-2.29). CONCLUSIONS: Less than daily intake of whole milk was associated with a statistically significant, although modest, lower risk of CVD compared with non-consumption, but this potential benefit may not extend to daily intake in this population.

Potential Severe Asthma Hidden in UK Primary Care.

BACKGROUND: Severe asthma may be underrecognized in primary care. OBJECTIVE: Identify and quantify patients with potential severe asthma (PSA) in UK primary care, the proportion not referred, and compare primary care patients with PSA with patients with confirmed severe asthma from UK tertiary care. METHODS: This was a historical cohort study including patients from the Optimum Patient Care Research Database (aged ≥16 years, active asthma diagnosis pre-2014) and UK patients in the International Severe Asthma Registry (UK-ISAR aged ≥18 years, confirmed severe asthma in tertiary care). In the OPCRD, PSA was defined as Global INitiative for Asthma 2018 step 4 treatment and 2 or more exacerbations/y or at Global INitiative for Asthma step 5. The proportion of these patients and their referral status in the last year were quantified. Demographic and clinical characteristics of groups were compared. RESULTS: Of 207,557 Optimum Patient Care Research Database patients with asthma, 16,409 (8%) had PSA. Of these, 72% had no referral/specialist review in the past year. Referred patients with PSA tended to have greater prevalence of inhaled corticosteroid/long-acting ß2-agonist add-ons (54.1 vs 39.8%), and experienced significantly (P < .001) more exacerbations per year (median, 3 vs 2/y), worse asthma control, and worse lung function (% predicted postbronchodilator FEV1/forced vital capacity, 0.69 vs 0.72) versus nonreferred patients. Confirmed patients with severe asthma (ie, UK patients in the International Severe Asthma Registry) were younger (51 vs 65 years; P < .001), and significantly (P < .001) more likely to have uncontrolled asthma (91.4% vs 62.5%), a higher exacerbation rate (4/y [initial assessment] vs 3/y), use inhaled corticosteroid/long-acting ß2-agonist add-ons (67.7% vs 54.1%), and have nasal polyposis (24.2% vs 6.8) than referred patients with PSA. CONCLUSIONS: Large numbers of patients with PSA in the United Kingdom are underrecognized in primary care. These patients would benefit from a more systematic assessment in primary care and possible specialist referral.

Eosinophilic and Noneosinophilic Asthma: An Expert Consensus Framework to Characterize Phenotypes in a Global Real-Life Severe Asthma Cohort.

BACKGROUND: Phenotypic characteristics of patients with eosinophilic and noneosinophilic asthma are not well characterized in global, real-life severe asthma cohorts. RESEARCH QUESTION: What is the prevalence of eosinophilic and noneosinophilic phenotypes in the population with severe asthma, and can these phenotypes be differentiated by clinical and biomarker variables? STUDY DESIGN AND METHODS: This was an historical registry study. Adult patients with severe asthma and available blood eosinophil count (BEC) from 11 countries enrolled in the International Severe Asthma Registry (January 1, 2015-September 30, 2019) were categorized according to likelihood of eosinophilic phenotype using a predefined gradient eosinophilic algorithm based on highest BEC, long-term oral corticosteroid use, elevated fractional exhaled nitric oxide, nasal polyps, and adult-onset asthma. Demographic and clinical characteristics were defined at baseline (ie, 1 year before or closest to date of BEC). RESULTS: One thousand seven hundred sixteen patients with prospective data were included; 83.8% were identified as most likely (grade 3), 8.3% were identified as likely (grade 2), and 6.3% identified as least likely (grade 1) to have an eosinophilic phenotype, and 1.6% of patients showed a noneosinophilic phenotype (grade 0). Eosinophilic phenotype patients (ie, grades 2 or 3) showed later asthma onset (29.1 years vs 6.7 years; P < .001) and worse lung function (postbronchodilator % predicted FEV1, 76.1% vs 89.3%; P = .027) than those with a noneosinophilic phenotype. Patients with noneosinophilic phenotypes were more likely to be women (81.5% vs 62.9%; P = .047), to have eczema (20.8% vs 8.5%; P = .003), and to use anti-IgE (32.1% vs 13.4%; P = .004) and leukotriene receptor antagonists (50.0% vs 28.0%; P = .011) add-on therapy. INTERPRETATION: According to this multicomponent, consensus-driven, and evidence-based eosinophil gradient algorithm (using variables readily accessible in real life), the severe asthma eosinophilic phenotype was more prevalent than previously identified and was phenotypically distinct. This pragmatic gradient algorithm uses variables readily accessible in primary and specialist care, addressing inherent issues of phenotype heterogeneity and phenotype instability. Identification of treatable traits across phenotypes should improve therapeutic precision.

Characterization of Severe Asthma Worldwide: Data From the International Severe Asthma Registry.

BACKGROUND: Clinical characteristics of the international population with severe asthma are unknown. Intercountry comparisons are hindered by variable data collection within regional and national severe asthma registries. We aimed to describe demographic and clinical characteristics of patients treated in severe asthma services in the United States, Europe, and the Asia-Pacific region. METHODS: The International Severe Asthma Registry retrospectively and prospectively collected data in patients with severe asthma (≥ 18 years old), receiving Global Initiative for Asthma (GINA) Step 5 treatment or with severe asthma remaining uncontrolled at GINA Step 4. Baseline demographic and clinical data were collected from the United States, United Kingdom, South Korea, Italy, and the Severe Asthma Web-based Database registry (including Australia, Singapore, and New Zealand) from December 2014 to December 2017. RESULTS: We included 4,990 patients. Mean (SD) age was 55.0 (15.9) years, and mean (SD) age at asthma onset was 30.7 (17.7) years. Patients were predominantly female (59.3%) and white (72.6%), had never smoked (60.5%), and were overweight or obese (70.4%); 34.9% were at GINA Step 5; and 57.2% had poorly controlled disease. A total of 51.1% of patients were receiving regular intermittent oral corticosteroids, and 25.4% were receiving biologics (72.6% for those at GINA Step 5). Mean (SD) exacerbation rate was 1.7 (2.7) per year. Intercountry variation was observed in clinical characteristics, prescribed treatments, and biomarker profiles. CONCLUSIONS: Using a common data set and definitions, this study describes severe asthma characteristics of a large patient cohort included in multiple severe asthma registries and identifies country differences. Whether these are related to underlying epidemiological factors, environmental factors, phenotypes, asthma management systems, treatment access, and/or cultural factors requires further study.

Association of "Elevated Blood Pressure" and "Stage 1 Hypertension" With Cardiovascular Mortality Among an Asian Population.

BACKGROUND: The new American College of Cardiology/American Heart Association high blood pressure (BP) guidelines in the United States have lowered definition of hypertension by defining normal as systolic/diastolic BP <120/80 mm Hg; elevated BP as systolic between 120 and 129 mm Hg and diastolic <80 mm Hg; and stage 1 hypertension as systolic between 130 and 139 mm Hg or diastolic between 80 and 89 mm Hg. METHODS AND RESULTS: We investigated the association between the new hypertension definition and cardiovascular disease mortality among Chinese in Singapore. We used data from 30 636 participants of a population-based cohort, the SCHS (Singapore Chinese Health Study), who had BPs measured using a standard protocol at ages 46 to 85 years between 1994 and 2005. Information on lifestyle factors was collected at recruitment (1993-1998) and follow-up 1 interviews (1999 and 2004). Mortality was identified via nationwide registry linkage up to December 31, 2016. Neither elevated BP (hazard ratio, 0.89; 95% confidence interval, 0.74-1.07) nor stage 1 hypertension (hazard ratio, 0.94; 95% confidence interval, 0.81-1.11) was associated with increased risk of cardiovascular mortality compared with normal BP in the whole cohort. Stage 1 hypertension was associated with increased cardiovascular risk only in those <65 years of age and without a history of cardiovascular disease (hazard ratio, 1.40; 95% confidence interval, 1.01-1.94), but not in those ≥65 years of age or with a history of cardiovascular disease. CONCLUSIONS: Our data suggest that the newly defined stage 1 hypertension may not be associated with increased cardiovascular mortality across all ages among Chinese in Singapore, but that the at-risk subpopulation is limited to those <65 years of age and without a prior cardiovascular disease.

Determinants of Incident Metabolic Syndrome in a Middle Eastern Population: Isfahan Cohort Study.

BACKGROUND: To identify the associated risk factors with development of metabolic syndrome (MetS) in a longitudinal prospective cohort study in an Iranian population. METHODS: A total of 1994 participants, aged ≥35 years, free of MetS, diabetes, and cardiovascular disease at baseline were followed up for 7 years. Physical examination, laboratory studies, and interview about lifestyle factors were performed, and MetS was defined based on harmonized definition at both time points. Logistic regression was used to calculate odds ratio (OR) and corresponding 95% confidence interval (CI). RESULTS: MetS occurred in 27% of subjects with an incidence rate of 39.2 and 46.6 per 1000 person-year in men and women, respectively (P = 0.04). Among the components of MetS, triglyceride (TG) alone (OR 2.59, 95% CI 1.78-3.78) or in combination with waist circumference (WC; OR 5.01, 95% CI 3.59-7.01) was the strongest predictor of incident MetS compared to those free of components. In multivariable analysis, all components were associated with higher risk except fasting plasma glucose in both genders and high-density lipoprotein cholesterol in men. Impaired glucose tolerance was associated with two (95% CI 1.11-3.65) times increased risk in women. The multivariable adjusted OR (95% CI) of overweight and obesity was 1.68 (1.13-2.50) and 2.88 (1.73-4.78) in women and 2.46 (1.74-3.46) and 2.47 (1.38-4.43) in men, respectively. Unhealthy diet [1.57 (1.02-2.41)] and weekly Cola consumption [1.50 (1.05, 2.14)] increased the risk in women only. CONCLUSIONS: TG and WC components showed the highest predictive values for MetS incidence, while general obesity was independently associated with it.

Sleep quality in women with systemic lupus erythematosus: contributing factors and effects on health-related quality of life.

AIM: Sleep quality disturbances are common in patients with systemic lupus erythematosus (SLE). We evaluated sleep quality and its contributors in women with SLE. Also we evaluated the effects of sleep quality disturbance on patients' health-related quality of life (HRQoL). METHODS: Sleep quality was assessed in 77 women with SLE (age 36.5 ± 10.1 years) using the Pittsburgh Sleep Quality Index (PSQI). Disease activity and cumulative disease damage were assessed with standard indices. Patients completed the Hospital Anxiety and Depression Scale and LupusQoL. Univariate and multivariate analyses were performed to find contributors of poor sleep quality and association of sleep quality with HRQoL. RESULTS: Poor sleep quality was present in 44 patients (57.1%). Poor sleepers were older (P = 0.015) and had higher body mass index (P = 0.027) and more severe anxiety (P < 0.001) and depression symptoms (P < 0.007) compared with good sleepers. In the logistic regression model, age (ß = 1.16, P = 0.006), disease activity (ß = 1.10, P = 0.050), and anxiety/depression composite score (ß = 1.16, P = 0.008) were independent contributors of poor sleep quality. Poor sleepers had impaired HRQoL in almost all domains of the LupusQoL than good sleepers (P < 0.05). CONCLUSION: Poor sleep quality is common in women with SLE and significantly impairs their HRQoL. Age, disease activity and psychological factors were determinants of sleep quality in our study. Studies with objective sleep measures as well as interventional studies are warranted in this regard.