Background We have previously described that fraction of exhaled nitric oxide (F eno ) levels and blood eosinophil counts offer additive information in relation to asthma and asthma exacerbations ...when analyzing data from a large population study. Objective We sought to investigate increased F eno levels and blood eosinophil counts in relation to lung function, bronchial hyperresponsiveness (BHR), and asthma control in a cohort of young asthmatic patients. Methods Measurements of F eno levels and blood eosinophil counts were available in 406 subjects (208 women) aged 10 to 35 years. Asthma control was assessed through the Asthma Control Test. Moderate-to-severe BHR was defined as a cumulative dose of methacholine of less than 0.3 mg causing an FEV1 decrease of 20%. Results Subjects with simultaneously increased F eno levels (≥20-25 ppb) and blood eosinophil counts (≥0.3 × 109 /L) had a higher prevalence of uncontrolled asthma (Asthma Control Test score, <20) than subjects with singly increased blood eosinophil counts (40.5% vs 21.1%, P = .01). This difference remained significant ( P = .006), and a significant difference was also found between subjects with both increased F eno levels and blood eosinophil counts and subjects with normal F eno levels and blood eosinophil counts ( P = .02) after adjusting for confounders. Having increased F eno levels and blood eosinophil counts related to a higher prevalence of moderate-to-severe BHR than having normal F eno levels and blood eosinophil counts or singly increased F eno levels or blood eosinophil counts (85.7% vs 35.8% or 63.3% or 60%, P < .05 all comparisons). Conclusion We have shown that simultaneously increased local (F eno ) and systemic (blood eosinophil) markers of type 2 inflammation related to a higher likelihood of BHR and uncontrolled asthma in a large cohort of young asthmatic patients.
If the denatured proteins can be folded when bound to a solid media in a chromatographic process, it may be a useful combination of simultaneous protein refolding and separation. ...we carefully ...designed the following strategies for experimental approach: Starting with lysozyme, an easily characterized and well documented protein, as the model but aiming at solving the real problems of genetically engineered inclusion body proteins, such as granulocyte colony stimulating factor (GCSF), interferons, single chain antibody (scFV), non-glycosylation erythropoietin (ngEPO). Concept of the protein refolding in ion exchange chromatography (IEC) or in hydrophobic interaction chromatography (HIC) TABLE 1 Comparison of two refolding methods for renaturation of recombinant human lysozyme Item of comparison Dilution refolding IEC refolding Process time (h) 2 Final protein concentration (mg/mL) 0.03 0.6 Protein recovery (%) 100 98 Activity recovery (%) 29 95 Specific activity (U/mg) 12,900 41,418 Summarizing the results of the above three chromatographic processes, a common protocol can be developed as shown in Figure 5 in which the column could be the SEC, the IEC, the HIC, or affinity (AC). Pharmaceutical companies approached us for help to solve their refolding problems of recombinant proteins, such as human single-chain antibodies, human lysozyme, Fe-SOD, human colony stimulating factor, alpha-interferon, Staphylococcus aureus prolongation factor G, etc.
Background Exercise-induced respiratory symptoms are common among adolescents. Exercise is a known stimulus for transient narrowing of the airways, such as exercise-induced bronchoconstriction (EIB) ...and exercise-induced laryngeal obstruction (EILO). Our aim was to investigate the prevalence of EIB and EILO in a general population of adolescents. Methods In this cross-sectional study, a questionnaire on exercise-induced dyspnoea was sent to all adolescents born in 1997 and 1998 in Uppsala, Sweden (n=3838). A random subsample of 146 adolescents (99 with self-reported exercise-induced dyspnoea and 47 without this condition) underwent standardised treadmill exercise tests for EIB and EILO. The exercise test for EIB was performed while breathing dry air; a positive test was defined as a decrease of ≥10% in FEV1 from baseline. EILO was investigated using continuous laryngoscopy during exercise. Results The estimated prevalence of EIB and EILO in the total population was 19.2% and 5.7%, respectively. No gender differences were found. In adolescents with exercise-induced dyspnoea, 39.8% had EIB, 6% had EILO and 4.8% had both conditions. In this group, significantly more boys than girls had neither EIB nor EILO (64.7% vs 38.8%; p=0.026). There were no significant differences in body mass index, lung function, diagnosed asthma or medication between the participants with exercise-induced dyspnoea who had or did not have a positive EIB or EILO test result. Conclusions Both EIB and EILO are common causes of exercise-induced dyspnoea in adolescents. EILO is equally common among girls and boys and can coexist with EIB.
Background
Patterns and determinants of long‐term oral corticosteroid (OCS) use in asthma and related morbidity and mortality are not well‐described. In a nationwide asthma cohort in Sweden, we ...evaluated the patterns and determinants of OCS use and risks of OCS‐related morbidities and mortality.
Methods
Data for 217 993 asthma patients (aged ≥ 6 years) in secondary care were identified between 2007 and 2014 using Swedish national health registries. OCS use at baseline was categorized: regular users (≥5 mg/d/y; n = 3299; 1.5%); periodic users (>0 but <5 mg/d/y; n = 49 930; 22.9%); and nonusers (0 mg/d/y; n = 164 765; 75.6%). Relative risks of becoming a regular OCS user and for morbidity and mortality were analysed using multivariable Cox regression.
Results
At baseline, 24% of asthma patients had used OCS during the last year and 1.5% were regular users. Of those not using OCS at baseline, 26% collected at least one OCS prescription and 1.3% became regular OCS users for at least 1 year during the median follow‐up of 5.3 years. Age at asthma diagnosis, increasing GINA severity and Charlson Comorbidity Index were associated with regular OCS use. Compared to periodic and non‐OCS use, regular use was associated with increased incidence of OCS‐related morbidities and greater all‐cause mortality, adjusted HR 1.34 (95% CI 1.24‐1.45).
Conclusions
Oral corticosteroids use is frequent for asthma patients, and many are regular users. Regular OCS use is associated with increased risk of morbidity and mortality. These findings indicate that there is a need of other treatment options for patients with severe asthma who are using regular OCS.
Annually, almost one in seven asthma patients used oral corticosteroids, which was stable over the 10‐year study period. Oral corticosteroids are still a substantial part of current asthma management for many patients and are associated with severe side effects and mortality risk. There is a need for other treatments for severe asthma patients who are using regular oral corticosteroids.
Inhaled therapies are the cornerstone of treatment in asthma and chronic obstructive pulmonary disease, and there are a multitude of devices available. There is, however, a distinct lack of ...evidence-based guidance for healthcare providers on how to choose an appropriate inhaler. This review aims to summarise recent updates on topics related to inhaler choice, and to offer practical considerations for healthcare providers regarding currently marketed devices. The importance of choosing the right inhaler for the right patient is discussed, and the relative merits of dry powder inhalers, pressurised metered dose inhalers, breath-actuated pressurised metered dose inhalers, spacers and soft mist inhalers are considered. Compiling the latest studies in the devices therapy area, this review focuses on the most common types of handling errors, as well as the comparative rates of incorrect inhalation technique between devices. The impact of device-specific handling errors on inhaler performance is also discussed, and the characteristics that can impair optimal drug delivery, such as inhalation flow rate, inhalation volume and particle size, are compared between devices. The impact of patient perceptions, behaviours and problems with inhalation technique is analysed, and the need for appropriate patient education is also highlighted. The continued development of technology in inhaler design and the need to standardise study assessment, endpoints and patient populations are identified as future research needs.
The reviews of this paper are available via the supplemental material section.
Bronchodilator response (BDR) testing is used as a diagnostic method in obstructive airway diseases. The aim of this investigation was to compare different methods for measuring BDR in participants ...with asthma and chronic obstructive pulmonary disease (COPD) and to study to the extent to which BDR was related to symptom burden and phenotypic characteristics.Forced expiratory volume in 1 s (FEV
) and forced vital capacity (FVC) were measured before and 15 min after 200 μg of salbutamol in 35 628 subjects aged ≥16 years from three large international population studies. The subjects were categorised in three groups: current asthma (n=2833), COPD (n=1146) and no airway disease (n=31 649). Three definitions for flow-related reversibility (increase in FEV
) and three for volume-related reversibility (increase in FVC) were used.The prevalence of bronchodilator reversibility expressed as increase FEV
≥12% and 200 mL was 17.3% and 18.4% in participants with asthma and COPD, respectively, while the corresponding prevalence was 5.1% in those with no airway disease. In asthma, bronchodilator reversibility was associated with wheeze (OR 1.36, 95% CI 1.04-1.79), atopy (OR 1.36, 95% CI 1.04-1.79) and higher exhaled nitric oxide fraction, while in COPD neither flow- nor volume-related bronchodilator reversibility was associated with symptom burden, exacerbations or health status after adjusting for pre-bronchodilator FEV
Bronchodilator reversibility was at least as common in participants with COPD as those with asthma. This indicates that measures of reversibility are of limited value for distinguishing asthma from COPD in population studies. However, in asthma, bronchodilator reversibility may be a phenotypic marker.
Highlights • The role of obesity and weight gain in the development of sleep problems in a population-based cohort was studied. • Overweight and obese subjects reported more sleep problems at ...baseline. • There was no independent association between body mass index (BMI) level at baseline and development of new sleep problems. • Weight gain was an independent risk factor for developing several sleep problems and daytime sleepiness.
The prevalence of diabetes mellitus is growing globally and the management of diabetes is a critical issue for public health. This study aimed to analyze the concentration of different biomarkers in ...patients with type 2 diabetes mellitus (T2DM) without complication, T2DM patients with complication (T2DM+C), and compared to healthy controls (HC). For this aim, there were 164 participants: 59 T2DM, 60 T2DM+C, and 45 HC. Venous blood was collected and the levels of Hemoglobin A1C (HbA1C), fasting blood glucose, Interleukin-31 (IL-31), IL-35, glutamic acid decarboxylase antibody (GADA), developmental locus-1 (Del-1), fibroblast growth factor-9 (FGF-9) and FGF-18) and lipid profile (total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL) and triglyceride) were analyzed. Results showed that IL-31 was significantly higher in T2DM compared to HC (p<0.0001), and compared to T2DM+C (p<0.0001). IL-31 was significantly lower in T2DM+C than HC (p=0.009). The level of serum GADA was significantly elevated in T2DM compared to HC (p=0.0009), and T2DM+C (p=0.03). There was a significant correlation between (IL-31, IL-35, GADA, Del-1, FGF-9 and FGF-18). The duration of having diabetes was significantly longer in T2DM+C compared to T2DM (p<0.0001). However, there was no significant difference in the level of HBA1C% between T2DM+C and T2DM patients (p=0.98). In conclusion, there were significant differences in biomarker concentrations between all three groups. This indicates that the monitoring of multiple biomarkers may be of value in the controlling of T2DM in the future.
Background Fraction of exhaled nitric oxide (F eno ) and blood eosinophil count (B-Eos) values, markers of local and systemic eosinophilic inflammation, respectively, are increased in asthmatic ...patients. Little is known about the relation of these markers to reported wheeze and asthma events in a random population sample. Objectives We sought to determine the individual and independent values of B-Eos and F eno in relation to wheeze, asthma diagnosis, and asthma events in a cross-sectional study. Methods F eno and B-Eos values were measured in 12,408 subjects aged 6 to 80 years from the National Health and Nutrition Examination Survey 2007-2008 and 2009-2010. Current wheeze and asthma diagnosis, as well as asthma attacks and asthma-related emergency department (ED) visits within the last 12 months, were assessed by means of questionnaires. Results Intermediate or high F eno values and intermediate or high B-Eos values were independently associated with having asthma, wheeze, and asthma attacks. However, only intermediate and high B-Eos values were independently associated with asthma-related ED visits. High F eno (≥50 ppb) and B-Eos (≥500 cells/mm3 ) values rendered an adjusted odds ratio of 4.5 of having wheeze, 5.1 of having asthma, 5.4 for asthma attacks, and 2.9 for asthma-related ED visits compared with normal F eno (<25 ppb) and B-Eos (<300 cells/mm3 ) values. Conclusions Exhaled nitric oxide and B-Eos values offered independent information in relation to the prevalence of wheeze, asthma diagnosis, and asthma events in this random population sample. The clinical importance of these findings in asthmatic patients with regard to phenotyping and individualized treatment, considering both local and systemic eosinophilic inflammation, needs to be determined.
Chronic breathlessness is a dominating symptom that restricts daily life for many people with cardiorespiratory disease 1. Different dimensions of the symptom, such as the intensity, sensory ...qualities and emotional responses, can be assessed using the instruments Dyspnea-12 (D-12) 2 and the Multidimensional Dyspnea Profile (MDP) 3, which share similarities in the underlying constructs of what is measured 4 and have emerged as widely used instruments for multi-dimensional measurement of breathlessness
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