The impact of multistrains of probiotics on Th17-related cytokines in patients with asthma: a randomized, double-blind, placebo-controlled trial.

OBJECTIVE: Asthma is known as one of the most common chronic inflammatory diseases characterized by recurrent obstruction and inflammation of the airways. Probiotics are defined as a group of beneficial living microorganisms that are beneficial in many disorders, including allergies. The aim of this study was to investigate the probiotic supplement effects on improvement of clinical asthma symptom and changes in the pattern of Th17-related inflammatory cytokines in asthmatic patients. METHODS: This was a randomized controlled clinical trial with parallel, double-blind groups. Forty patients with asthma were enrolled and received 1 capsule/day of a probiotic supplement for 8 weeks. Respiratory function tests; and the level of IL-6, IL-17, IL-21 and TGF-ß were evaluated at the baseline and end of intervention. RESULTS: The results showed that the level of IL-6 and IL-17 in patients after receiving probiotics was reduced and expression of TGF-ß was increased as compared to the baseline. Also, the expression of IL-17 and IL-21 in the probiotic group was significantly lower than the placebo group at the end of the intervention. In addition, an improvement in pulmonary function tests and clinical symptoms was observed after receiving probiotics. CONCLUSIONS: Eight-weeks treatment with a probiotic supplementation suggests that it may effect on Th17 cells-associated IL-6, IL-17 and TGF-ß; and Forced Expiratory Volume in 1 s and Forced Vital Capacity. Taken together, these results suggest that probiotics may have the ability to affect neutrophilic asthma and they can possibly be used besides common treatments for patients with neutrophilic asthma.

Anti-IL-5/5Ra biologics improve work productivity and activity in severe asthma: a RAPSODI registry-based cohort study.

INTRODUCTION: Severe asthma is associated with a serious disease burden, partially caused by limitations in activity and work impairment. AIMS AND OBJECTIVES: This study aims to relate treatment with biologics targeting IL-5/5Ra to work productivity and activity in the long term in a real-world context. MATERIAL AND METHODS: This is a registry-based multi-center cohort study evaluating data from adults with severe eosinophilic asthma included in the Dutch Register of Adult Patients with Severe Asthma for Optimal DIsease management (RAPSODI). Patients that started with anti-IL-5/5Ra biologics and completed the work productivity and activity improvement questionnaire, were included. Study and patient characteristics were compared between the employed and unemployed patients. Work productivity and activity impairment are related to accompanying improvements in clinical outcomes. RESULTS: At baseline, 91 of 137 patients (66%) were employed which remained stable throughout the follow-up period. Patients in the working age category were younger and had significantly better asthma control (p = 0.02). Mean overall work impairment due to health decreased significantly from 25.5% (SD2.6) to 17.6% (SD 2.8) during 12 months anti-IL-5/5Ra biologics treatment (P = 0.010). There was a significant association between ACQ6 and overall work improvement after targeted therapy (ß = 8.7, CI 2.1-15.4, P = 0.01). The improvement of asthma control of 0.5 points on the asthma Control Questionnaire was associated with an overall work impairment of -9%. CONCLUSIONS: Work productivity and activity in severe eosinophilic asthma improved after starting anti-IL-5/5Ra biologics. Clinically relevant improvement in asthma control was associated with an overall work impairment score of -9% in this study.

Assessing the validity and reliability of the Arabic versions of Mini Asthma Quality of life questionnaire and Asthma Control Test in adult patients with asthma: A factor analysis study.

Background and objective: Asthma is a common disease that has a significant influence on patients' quality of life. Although Arabic tools for assessing symptom control and quality of life in individuals with asthma are available, no sufficient studies have evaluated the validity of these tools. Therefore, the aim of the current study was to validate the Arabic version of these tools. Methods: Exploratory Factor Analysis (EFA) and Confirmatory Factor Analysis (CFA) were conducted on the Arabic versions of the Asthma Control Test (ACT) and Mini Asthma Quality of Life Questionnaire (Mini AQLQ). Results: A total of 314 participants (70.1 % females) were enrolled in the current study. The mean age of the participants was 51.47 (±16.37). EFA suggested a three-factor model for Mini AQLQ and a one-factor model for ACT, which was confirmed by CFA analyses. High correlations were found between spirometric values and ACT and Mini AQLQ scores, indicating good concurrent validity. The area under the curve produced by the Roc curve was 0.861 (p < 0.001), and the most suitable cut-off point was 4.741. Conclusion: All analyses conducted showed that the Arabic versions of both Mini AQLQ and ACT are reliable and valid and can be administered to adults with asthma. The application of these validated instruments will improve the management and diagnosis of asthma in Arab countries.

Benralizumab improves patient reported outcomes and functional parameters in difficult-to-treat patients with severe asthma: Data from a real-life cohort.

In the last decade, an increasing number of randomized controlled trials (RCTs) on biologic therapy in patients with severe asthma have included patient-reported outcomes (PROs) as secondary efficacy measures. The majority of these RCTs showed a benefit in symptoms and quality of life. However, the magnitude of this benefit remains uncertain, because it rarely exceeded the minimal important difference (MID), owing to a significant improvement in the control group (placebo effect). Real-life studies on biologic therapies assessing PRO are scarce. They may support and integrate RCT results through their different experimental design. This real-life retrospective study provides data on 15 patients with difficult-to-treat severe eosinophilic asthma treated with benralizumab up to 6 months. Asthma quality of life questionnaire (AQLQ) and asthma control test (ACT) were assessed and administered at each visit to minimize the Hawthorne effect. Changes in general accepted efficacy measures, such as forced expiratory volume in 1 s (FEV1), peak expiratory flux (PEF), exacerbation rate and blood eosinophils, from baseline were also assessed. AQLQ and ACT improved from 3.9 ± 0.4 to 5.2 ± 0.4 and from 15.6 ± 5.7 to 18.1 ± 5.6, respectively. FEV1 increased of about 250 ml (+14%). PEF increased from 288 ± 107 to 333 ± 133 l/min. The number of exacerbations requiring OCS courses decreased from 2.8 ± 2.2 to 0.5 ± 0.8. Eosinophil counts dropped to 25.6 ± 15 cells/microliter. In conclusion, most patients reported improvements in AQLQ and ACT greater than MID, suggesting that these outcome represent a sensitive tool in real-life effectiveness studies. Our approach reduced the limitations of transition questions and the Hawthorne effect, increasing findings reliability.

Main Contributory Factors on Asthma Control and Health-Related Quality of Life in Elderly Asthmatics.

OBJECTIVE: To assess the main factors involved in asthma control and health-related quality of life in elderly asthmatic patients. METHODS: We performed a retrospective case-control study nested in a historical cohort that compared patients who had partly controlled or uncontrolled asthma (Asthma Control Test [ACT] score ≤19) (cases) with patients who had well-controlled asthma (ACT ≥20) (controls). Clinical data were collected from medical records. Outcomes included ACT score and health-related quality of life (Asthma-Specific Quality of Life Questionnaire [AQLQ]). Pulmonary function was determined by spirometry. RESULTS: We evaluated 209 asthma patients (151 women) aged ≥65 years. Mean age was 73.55 years. Most patients had persistent moderate (47.60%) or severe (47.12%) asthma. A total ACT score ≤19 was obtained in 64 (30.62%) patients. Lack of adherence to treatment and presence of severe exacerbations were risk factors for partly controlled/uncontrolled asthma (OR, 8.33 and 5.29, respectively). In addition, for each additional unit score in the AQLQ, the risk of poor control increased by 1.51. The factors influencing the AQLQ score were asthma control (ACT) and presence of comorbidities such as depression, gastroesophageal reflux disease, and osteoporosis. CONCLUSIONS: Despite receiving antiasthma therapy, almost one-third of elderly patients had uncontrolled asthma, possibly as a result of poor adherence, exacerbations, and reduced health-related quality of life. Nonrespiratory comorbid conditions in older patients do not seem to be associated with worse control of asthma symptoms, although their effect on health-related quality of life could indirectly affect asthma control.

How does the EQ-5D-5L perform in asthma patients compared with an asthma-specific quality of life questionnaire?

BACKGROUND: Asthma patients experience impairments in health-related quality of life (HRQL). Interventions are available to improve HRQL. EQ-5D-5L is a common generic tool used to evaluate health interventions. However, there is debate over whether the use of this measure is adequate in asthma patients. METHODS: We used data from 371 asthma patients participating in a pulmonary rehabilitation (PR) program from the EPRA randomized controlled trial. We used four time points: T0 randomization, T1 start PR, T2 end PR, T3 3 months follow-up. We calculated floor and ceiling effects, intra-class correlation (ICC), Cohen's d, and regression analysis to measure the sensitivity to changes of EQ-5D-5 L (EQ-5D index and Visual Analog Scale (VAS)) and the disease-specific Asthma Quality of Life Questionnaire (AQLQ). Furthermore, we estimated the minimally important difference (MID). Based on the Asthma Control Test (ACT) scores, we defined three groups: 1. ACT-A (ACT> 19) controlled asthma, 2. ACT-B (14 < ACT≤19) not well-controlled asthma, and 3. ACT-C (ACT≤14) very poorly controlled asthma. RESULTS: Only the EQ-5D index showed ceiling effects at T2 and T3 (32%). ICC (between T0 and T1) was moderate or good for all measures. Cohen's d at T2 and T3 was better at differentiating between ACT-A and ACT-B than between ACT-B and ACT-C. The EQ-5D index showed moderate effect sizes (0.63-0.75), while AQLQ showed large effect sizes (0.74-1,48). VAS was responsive to pronounced positive and negative ACT changes in every period, and AQLQ mostly to the positive changes, whereas the EQ-5D index was less responsive. We estimated a MID of 0.08 for the EQ-5D index, 12.3 for VAS, and 0.65 for AQLQ. CONCLUSION: All presented HRQL tools had good discriminatory power and good reliability. However, EQ-5D-5 L did not react very sensitively to small changes in asthma control. Therefore, we would suggest using supplementary measures in addition to EQ-5D-5 L to evaluate asthma-specific interventions more comprehensively. TRIAL REGISTRATION: German Clinical Trial Register, DRKS00007740 (date of registration: 05/15/2015), https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00007740. The registration took place prospectively.

[The quality of life and accessibility of medical care in persons with bronchial asthma in the Republic of Kazakhstan].

The access barriers to asthma basic treatment and medical care in many countries are an urgent problem and emphasize the need for population studies to examine the associated risk factors for barriers to health care, causes of severe exacerbations, disruption of life quality, and the development of preventive measures. The purpose of study was to evaluate the association of quality of life, access to medical care and emergency of severe exacerbation in persons with bronchial asthma in the Republic of Kazakhstan. The cross-sectional study was applied. The sample included 3,572 patients of both genders aged 18-59 years with bronchial asthma, registered in out-patient clinics of the Republic of Kazakhstan. The assessment of frequency of severe exacerbation in patients with asthma, depending on availability of medical care, demonstrated significant differences in groups of minimal, average and maximum decrease (χ2 = 160.66, 2057.06, 166.19, p<0.001). The most of patients in group with severe asthma exacerbations more than 3 times per year had signs of a maximum decrease in access to medical care - 53.5% and 42.11% were classified as a medium-level barrier of access. The indicator of quality of life was significantly lower in group of patients with severe exacerbation of disease more than 3 times per year in groups with severe access barriers as compared to group with similar number of exacerbations where the number of barriers was less than two - 10.85 vs. 15, 28 (t = 3.985, D.f. = 1, p = 0.003). The study permitted to conclude that improving quality and increasing availability of medical care of asthmatic patient is the key to managing course of asthma at stage of diagnosis and during treatment as well.

Impact of shared decision making on asthma quality of life and asthma control among children.

OBJECTIVE: Few studies have examined the effectiveness of shared decision making (SDM) in clinical practice. This study evaluated the impact of SDM on quality of life and symptom control in children with asthma. METHODS: We conducted a prospective 3-year study in six community-based practices serving a low-income patient population. Practices received training on SDM using an evidence-based toolkit. Patients aged 2-17 with a diagnosis of asthma were identified from scheduling and billing data. At approximate 6-month intervals, patients completed a survey consisting of the Mini Pediatric Asthma Quality of Life Questionnaire (range 1-7) and the control domain of the Pediatric Asthma Therapy Assessment Questionnaire (range 0-7). We used propensity scores to match 46 children receiving SDM to 46 children receiving usual care with decision support. Included children had completed a baseline survey and at least one follow-up survey. Random coefficient models incorporated repeated measures to assess the effect of SDM on asthma quality of life and asthma control. RESULTS: The sample was primarily of non-White patients (94.6%) with Medicaid insurance (92.4%). Receipt of SDM using an evidence-based toolkit was associated with higher asthma quality of life [mean difference 0.9; 95% confidence interval (CI) 0.4-1.4] and fewer asthma control problems (mean difference -0.9; 95% CI -1.6--0.2) compared to usual care with decision support. CONCLUSIONS: Implementation of SDM within clinical practices using a standardized toolkit is associated with improved asthma quality of life and asthma control for low-income children with asthma when compared to usual care with decision support.

Characteristics of asthmatic patients with and without repeat emergency department visits at an inner city hospital.

UNLABELLED: Abstract Objective: The objective of this study was to document the frequency and clinical characteristics associated with repeat emergency department (ED) visits for asthma in an inner city population with a high burden of asthma. METHODS: During an ED visit for asthma in an inner city hospital ('index visit'), patients completed a valid survey addressing disease and behavioral factors. Hospital records were reviewed for information about ED visits and hospitalizations for asthma during the 12 months before and the 90 days after the index visit. RESULTS: One hundred and ninety-two patients were enrolled; the mean age was 42 years, 69% were women, 36% were black, 54% were Latino, 69% had Medicaid, and 17% were uninsured. 100 patients (52%) were treated and released from the ED, 88 patients (46%) were hospitalized, and 4 patients (2%) left against medical advice. During the subsequent 90 days, 64 patients (33%) had at least one repeat ED visit for asthma and 27 (14%) were hospitalized for asthma. In a multivariate model, more past ED visits (OR 1.7, 95% CI 1.4, 2.1; p < 0.0001) and male gender (OR 2.5, 95% CI 1.2, 5.4; p = 0.02) remained associated with having a repeat ED visit. Most patients had the first repeat ED visit within 30 days and 18 returned within only 7 days. Among all patients with a repeat visit, those who were not hospitalized for the index visit were more likely to have a repeat visit within 7 days (37%) compared to those who were hospitalized (17%) (p = 0.05 in multivariate analysis). CONCLUSIONS: Repeat ED visits were prevalent among inner city asthma patients and most occurred shortly after the index visit. The strongest predictors of repeat visits were male gender and more ED visits in the 12 months before the index visit.

Bronchial thermoplasty: Long-term safety and effectiveness in patients with severe persistent asthma.

BACKGROUND: Bronchial thermoplasty (BT) has previously been shown to improve asthma control out to 2 years in patients with severe persistent asthma. OBJECTIVE: We sought to assess the effectiveness and safety of BT in asthmatic patients 5 years after therapy. METHODS: BT-treated subjects from the Asthma Intervention Research 2 trial (ClinicalTrials.govNCT01350414) were evaluated annually for 5 years to assess the long-term safety of BT and the durability of its treatment effect. Outcomes assessed after BT included severe exacerbations, adverse events, health care use, spirometric data, and high-resolution computed tomographic scans. RESULTS: One hundred sixty-two (85.3%) of 190 BT-treated subjects from the Asthma Intervention Research 2 trial completed 5 years of follow-up. The proportion of subjects experiencing severe exacerbations and emergency department (ED) visits and the rates of events in each of years 1 to 5 remained low and were less than those observed in the 12 months before BT treatment (average 5-year reduction in proportions: 44% for exacerbations and 78% for ED visits). Respiratory adverse events and respiratory-related hospitalizations remained unchanged in years 2 through 5 compared with the first year after BT. Prebronchodilator FEV1 values remained stable between years 1 and 5 after BT, despite a 18% reduction in average daily inhaled corticosteroid dose. High-resolution computed tomographic scans from baseline to 5 years after BT showed no structural abnormalities that could be attributed to BT. CONCLUSIONS: These data demonstrate the 5-year durability of the benefits of BT with regard to both asthma control (based on maintained reduction in severe exacerbations and ED visits for respiratory symptoms) and safety. BT has become an important addition to our treatment armamentarium and should be considered for patients with severe persistent asthma who remain symptomatic despite taking inhaled corticosteroids and long-acting ß2-agonists.

Dupilumab Efficacy in Patients With Uncontrolled or Oral Corticosteroid-Dependent Allergic and Nonallergic Asthma.

BACKGROUND: Type 2 cytokines IL-4/IL-5/IL-13 play an important role in pathogenesis of type 2 conditions, including asthma. Dupilumab, a human monoclonal antibody, blocks the shared receptor component for IL-4/IL-13, inhibiting signaling. In phase 2b (P2B) (NCT01854047) and phase 3 VENTURE (NCT02528214), dupilumab reduced annualized severe exacerbation rates (AER), improved forced expiratory volume in 1 second (FEV1), and was generally well tolerated in patients with uncontrolled, moderate-to-severe, or oral corticosteroid (OCS)-dependent severe asthma. OBJECTIVE: The post hoc assessment of dupilumab efficacy versus placebo in P2B and VENTURE in patients stratified by allergic status. METHODS: Allergic asthma was defined as total serum IgE ≥30 IU/mL and ≥1 perennial aeroallergen-specific IgE ≥0.35 kU/L at baseline. AER, prebronchodilator (BD) FEV1, FEV1/forced vital capacity (FVC) ratio, asthma control (5-item Asthma Control Questionnaire), health-related quality of life (HRQoL; Asthma Quality of Life Questionnaire), type 2 biomarkers, specific IgE, and OCS reduction (VENTURE only) were assessed. RESULTS: In patients with allergic asthma, dupilumab (P2B: pooled 200/300 mg; VENTURE: 300 mg) every 2 weeks versus placebo reduced AER (P2B: -60%, P < .01; VENTURE: -72%, P < .001), and, in P2B, increased pre-BD FEV1 (P < .01) and FEV1/FVC (P < .05). In both studies, dupilumab significantly improved asthma control and HRQoL and reduced most type 2 biomarkers. Dupilumab significantly reduced OCS use in VENTURE. Similar benefits were observed in patients without evidence of allergic asthma. CONCLUSIONS: Dupilumab significantly reduced AER and improved lung function, asthma control, and HRQoL in patients with or without evidence of allergic asthma.

The ATLAS ASMA Study: Assessing the Impact of Asthma on Patients' Life - The Spanish Patients' Perspective.

Purpose: ATLAS ASMA described the psychosocial impact of asthma on patients' daily life from patients' perspectives (in terms of impaired personal and intimate relationships, sleep quality, leisure time, daily activities, and others) in Spain. Secondary objective includes description of time since diagnosis, expectations, and satisfaction of patients about disease, treatment and medical assistance received, adherence to treatment, perceived control of asthma, and health-related quality of life. Patients and Methods: This was a cross-sectional, observational study, based on a self-administered online survey for adult patients (≥18 years) with asthma. Patients with asthma diagnosis of any type and severity who voluntarily participated in the survey through a web link were included consecutively. In the present manuscript, only adult patients' data are included. Results: A total of 132 adults with asthma were included. Moderate/severe asthma constituted 59.1% of the patients (females 71.2%). Overall, most relevant areas affected due to asthma were leisure activities (67.0%) and the quality/quantity of sleep (52.3%). Moderate/severe patients perceived some degree of impairment in work, school, or at home due asthma more frequently vs mild patients (55.2% vs 10.9%). Poorly controlled asthma (ACT≤19) was reported in 41 (70.7%) and 10 (21.7%) moderate/severe and mild patients (p<0.000), respectively. Mild patients obtained higher mean (SD) Mini-AQLQ score than moderate/severe asthma patients (5.6 [1.0] vs 4.3 [1.1], p<0.000), likewise higher significant results for every individual dimension. Most patients cited little limitation to intense efforts (20.5%). Half of the patients mentioned needing more information about asthma. Topics those patients like to have more information were difficulties that may can have and legal topics (78.6%), asthma evolution (78.6%), secondary effects or issues related to the treatment (61.9%) and legal topics (61.9%). Conclusion: The study reported important insights on psychosocial impact of asthma on patients' daily life from patients' perspectives along with health determinants in asthma-related health outcomes, sociodemographic and psychosocial factors.

Effectiveness of bronchial thermoplasty for severe persistent bronchial asthma accompanied by Pseudomonas aeruginosa infection.

Bronchial thermoplasty (BT) is a type of bronchoscopic treatment specifically used for patients with severe asthma. Most severe asthmatics receive systemic steroids and are at risk of being immunocompromised. This raises the clinical question of whether or not BT can be effectively and safely performed in such patients. Herein, we report a case highlighting the effectiveness and safety of BT in a patient with severe persistent bronchial asthma and Pseudomonas aeruginosa infection. We performed BT on a 46-year-old woman undergoing treatment for severe persistent asthma with inhaled steroids and 20 mg prednisolone orally. Although she was deemed to be infection-free before the procedure, culture of endobronchial secretions obtained during the first BT procedure grew Pseudomonas aeruginosa. After the first BT, she was given clarithromycin 400 mg orally daily. The amount of sputum decreased with each BT session, and sputum culture for Pseudomonas aeruginosa turned negative by the third BT session. Respiratory function tests showed 23.7% improvement in % post-bronchodilator forced expiratory volume in 1.0 s (%FEV1.0) and the asthma quality of life questionnaire (AQLQ) score increased by 2.41 points after the third BT. Bronchial wall thickness decreased and infiltrative shadows on CT disappeared after the three BT sessions, along with decrease in the amount of purulent sputum. Improvement in her asthma symptoms, after three BT sessions allowed decrease in the prednisolone dose. We report the effectiveness of BT and infection control in a severe asthmatic with Pseudomonas aeruginosa infection.

Fat mass to fat-free mass ratio and its associations with clinical characteristics in asthma.

BACKGROUND: Fat mass to fat-free mass ratio (FM/FFM) assesses the combined effect of the balance between fat mass and fat-free mass. AIMS: to evaluate the associations beetween FM/FFM and clinical outcomes in asthma and to compare clinical characteristics between individuals with higher and lower FM/FFM. METHODS: 128 participants with asthma underwent anthropometric, spirometry and bioelectrical impedance assessments. Physical activity in daily life (PADL) was assessed by the Actigraph for 7 days. Daily dose of inhaled medication, steps of pharmacological treatment, Asthma Control Questionnaire, Asthma Quality of Life Questionnaire and Hospital Anxiety and Depression Scale were also assessed. Participants were classified into two groups according to the 50th percentile of reference values for FM/FFM. RESULTS: Individuals with higher FM/FFM (n=75) used higher daily doses of inhaled corticosteroids, had worse lung function and fewer steps/day when compared to those with lower FM/FFM (n=53) (P≤0.021). Associations were found between absolute values of FM/FFM with lung function (FEV1 and FVC [liters]): R2=0.207 and 0.364;P<0.0001), and between the categories of lower or higher FM/FFM with steps of medication treatment (Cramer's V=0.218;P=0.016) and level of PADL (Cramer's V=0.236;P=0.009). The highest FM/FFM was a determining factor of physical inactivity (OR: 3.21;95%CI:1.17-8.78) and highest steps of pharmacological treatment (OR: 8.89;95%CI:1.23-64.08). CONCLUSION: Higher FM/FFM is significantly associated with worse clinical characteristics in individuals with asthma, such as higher doses of inhaled corticosteroids, worse lung function and fewer steps/day. Moreover, higher FM/FFM is a determining factor of physical inactivity and the highest steps of pharmacological treatment for asthma.

Fixed-dose combination of indacaterol/glycopyrronium/mometasone furoate once-daily versus salmeterol/fluticasone twice-daily plus tiotropium once-daily in patients with uncontrolled asthma: A randomised, Phase IIIb, non-inferiority study (ARGON).

BACKGROUND: The efficacy and safety of once-daily (o.d.) fixed-dose combination of indacaterol (IND), glycopyrronium (GLY) and mometasone furoate (MF) via Breezhaler® versus concurrent administration of salmeterol/fluticasone (SAL/FLU) twice-daily (b.i.d.) via Accuhaler®+Tiotropium (TIO) o.d. via Respimat® was evaluated in patients with uncontrolled asthma. METHODS: Patients (aged ≥18 years), symptomatic (Asthma Control Questionnaire [ACQ]-7 ≥1.5) despite treatment with long-acting ß2-agonist/inhaled corticosteroid medium- or high-dose, received IND/GLY/MF high- (150/50/160 µg) or medium-dose (150/50/80 µg) o.d. or SAL/FLU high-dose (50/500 µg) b.i.d.+Tio 5 µg o.d. for 24 weeks. The primary objective was to confirm the non-inferiority of either dose of IND/GLY/MF to SAL/FLU high dose + TIO in terms of Asthma Quality of Life Questionnaire (AQLQ). Additional endpoints: ACQ-7, lung function, health status (St George's Respiratory Questionnaire [SGRQ]), exacerbations, and safety after 24 weeks. RESULTS: IND/GLY/MF high- and medium-dose met the primary endpoint, confirming non-inferiority to SAL/FLU high dose + TIO for AQLQ (least square mean treatment difference [Δ]: 0.073 and -0.038, respectively; both p < 0.001). IND/GLY/MF high-dose improved ACQ-7 (Δ: -0.124; p = 0.004), trough FEV1 (Δ: 96 mL; p < 0.001), peak expiratory flow (morning [Δ: 9.56 L/min; p = 0.005], evening [Δ: 9.15 L/min; p = 0.006]) and SGRQ (Δ: -2.00; p = 0.04) versus SAL/FLU high dose + TIO. Improvements in these endpoints were comparable for IND/GLY/MF medium-dose and SAL/FLU high dose + TIO. Adverse events were generally comparable across treatments. CONCLUSIONS: IND/GLY/MF high- and medium-dose o.d. via a single inhaler were non-inferior to SAL/FLU high-dose b.i.d. + TIO o.d. via two inhalers for AQLQ. IND/GLY/MF high-dose o.d. improved lung function, asthma control and health status versus SAL/FLU high dose + TIO, while IND/GLY/MF medium-dose had comparable efficacy but at a corresponding lower steroid dose.

The association of exposure to PM10 with the quality of life in adult asthma patients.

OBJECTIVES: Air pollution has become a critical environmental issue, which severely threatens the well-being of asthma patients. The quality of life of these patients, when exposed to air pollutants such as particulate matter 10 (PM10), has been poorly studied. The current research examined the association between the concentration of PM10 in the air and the quality of life of patients with asthma. MATERIAL AND METHODS: The study group consisted of 300 adult asthma patients treated in 2 allergy outpatient clinics in Kraków, who declared they would not leave the city in the 14-day study period. Daily concentrations of PM10 from air monitoring stations were recorded over a period of 2 weeks, following which the patients filled out the standardized Asthma Quality of Life Questionnaire (AQLQ) regarding the monitored period to assess the total quality of life and its 4 domains (symptoms, limitation of activity, emotional functioning and environmental stimuli). RESULTS: The average PM10 exposure was 65.2 µg/m3 and only 30% of the patients were exposed to values of ≤50 µg/m3, i.e., the highest 24-h threshold value considered acceptable by the World Health Organization. The observed effect of an increased level of exposure to airborne PM10 was associated with reduced scores in AQLQ from 0.40 at the medium level to 0.46 at the high level, in comparison to the low level. The total score of the asthma-related quality of life and its domains showed poorer outcomes as the concentration of PM10 was increasing (every 0.08 pt per a 10 µg/m3 increase). CONCLUSIONS: The increase in the concentration of PM10 in the air impacts on the overall quality of life and its particular domains in people with exceptional predispositions, such as patients with bronchial asthma. Physicians taking care of asthma patients should pay special attention to the quality of patient's life in response to the course and control of that illness, in relation to air pollution. Int J Occup Med Environ Health. 2020;33(3):311-24.

Skin prick reactivity among asthmatics in East Africa.

BACKGROUND: The burden of asthma in Africa is high, and yet the disease is not universally prioritised. Data on allergic asthma and its impact on asthma morbidity are limited in Africa. Our aim was to describe the distribution of skin prick positivity among asthmatics in Eastern Africa. METHODS: From August 2016 to May 2018, 1671 asthmatic patients were enrolled from Uganda, Kenya, and Ethiopia as part of the African Severe Asthma Program clinical study. Skin prick testing was performed at baseline using a panel of 12 allergens, and factors associated with skin prick reactivity determined. RESULTS: Of the 1, 671 patients recruited, 71% were female with a median age of 40 years, 93.6% were aged >15 years and the patterns of asthma symptom frequency was intermittent in 2.9%, mild persistent in 19.9%, moderate persistent in 42.6% and severe persistent in 34.6% at baseline. Self-reported triggers, were dust (92%), cold weather (89%), upper respiratory infections (84%), strong smells (79%) and exposure to tobacco (78%). The majority (90%) of the participants had at least 1 positive allergen reaction, with 0.9% participants reacting to all the 12 allergens. Participants commonly reacted to house dust mites (66%), Blomia tropicalis (62%), and the German cockroach (52%). Patients sensitized to more allergens (>2) had significantly reduced lung function (FEV ≤ 80%; p = 0.001) and were more likely to visit the emergency department due to asthma (p = 0.012). There was no significant relationship between number of allergens and measures of asthma control, quality of life, and other clinical outcomes. Only the country of origin was independently associated with atopy among African asthmatics. CONCLUSION: There is a high prevalence of skin prick positivity among East African patients with asthma, with the commonest allergen being house dust mite. Skin reactivity did not correlate well with asthma severity and poor asthma control. The relation between atopy, measured through skin prick testing, and measures of asthma control among asthma patients in Eastern Africa is unclear and needs further study. TRIAL REGISTRATION: The ASAP study was registered prospectively. ClinicalTrials.gov Identifier: NCT03065920; Registration date: February 28, 2017; Last verified: February 28, 2017.

Efficacy predictors of omalizumab in Chinese patients with moderate-to-severe allergic asthma: Findings from a post-hoc analysis of a randomised phase III study.

BACKGROUND: Omalizumab has demonstrated efficacy as an add-on therapy in Chinese patients with moderate-to-severe allergic asthma. This post-hoc analysis assessed the potential predictors for the efficacy of omalizumab in these patients. METHODS: A post-hoc analysis was performed on a Phase III, randomised, controlled study conducted in Chinese patients with moderate-to-severe persistent allergic asthma (NCT01202903). We evaluated if levels of pre-treatment serum total immunoglobulin-E (IgE) and blood eosinophil (EOS), asthma severity, allergen profile, history of perennial allergic rhinitis (PAR), and free IgE level during omalizumab treatment were predictive of omalizumab's efficacy. RESULTS: This analysis included 608 patients (omalizumab, N = 306; placebo, N = 302). Improvements in forced expiratory volume in 1 s (FEV1), standardized Asthma Quality of Life Questionnaire (AQLQ), Asthma Control Questionnaire (ACQ), and Global Evaluation of Treatment Effectiveness (GETE) scores with omalizumab treatment compared with placebo were observed in patients with baseline IgE levels ≥76 IU/mL (irrespective of the EOS count). Relatively greater improvements with omalizumab treatment was also noted in patients with both moderate or severe allergic asthma (regardless of asthma severity), and patients sensitised to >3 allergens and with a history of PAR. All patients who were treated with omalizumab achieved free IgE levels below 50 ng/mL by Week 1. Similar clinical outcomes were observed in the subset of patients who achieved free IgE levels of <25 and ≥ 25 ng/mL. CONCLUSIONS: In Chinese patients with moderate-to-severe allergic asthma, baseline IgE and allergen profile (number/PAR history) are potential predictors of treatment response to omalizumab. TRIAL REGISTRATION: NCT01202903 (www.clinicaltrials.gov).

Living Well with Pollution? The Impact of the Concentration of PM2.5 on the Quality of Life of Patients with Asthma.

While the negative influence of environmental pollution on the respiratory system is well established, especially for people with bronchial hyper-reactivity, the impact of particulate matter on quality of life in asthma patients is not well understood. Three hundred adult asthma patients were recruited for a study; for each patient, the daily concentrations of particulate matter of 2.5 µm or less in diameter (PM2.5) were recorded from air quality monitoring stations. The study was conducted over two weeks. After two weeks, the patients filled out the Asthma Quality of Life Questionnaire (AQLQ), evaluating the quality of their lives throughout the monitored period. Patients exposed to a higher concentration of PM2.5 had significantly lower AQLQ scores. Every 10 µg/m3 of an increase in the concentration of PM2.5 resulted in a decrease of the AQLQ score by 0.16. All domains of quality of life (symptoms, activity limitations, emotional functioning, and environmental stimuli) assessed in the questionnaire were negatively affected by PM2.5. These findings provide an important argument in favor of educating physicians and patients and raising awareness about the detrimental health effects of air pollution. Improving the quality of life of people with asthma requires an immediate and substantial reduction of air pollution.

Time to onset of improvements in Quality of Life from Temperature-controlled Laminar Airflow (TLA) in severe allergic asthma.

BACKGROUND: Allergen avoidance is important in allergic asthma management. Nocturnal treatment with Temperature-controlled Laminar Airflow (TLA; Airsonett®) has been shown to provide significant reduction of exposure to allergens in the breathing zone, leading to long-term reduction in airway inflammation and improvement in quality of life. Allergic asthma patients uncontrolled on GINA step 4 were found to benefit the most. A frequently asked question from clinicians and funders is related to time to onset (TTO) of improvements for patients using TLA. METHODS: Asthma Quality of Life Questionnaire (AQLQ) scores were collected in a previous study. TTO of improvements in Quality of Life was analysed for difference (TLA-placebo) in Area-under-Curve using backwards deletion from 12, 9, 6, 3 down to 1 month for the AQLQ total score, the four individual domains and specifically the sleep question. RESULTS: Patients with uncontrolled asthma on GINA step 4 (n = 87)) reported a statistically significant and clinically relevant (≥0.5 point) improvement in total AQLQ score (0.57; p = 0.009) after 3 months treatment for TLA over placebo. The shortest TTO was within 1 month for the environmental domain (0.68; p = 0.016) and the sleep question (0.771; p = 0.037). TTO for the emotional and symptom domains was 3 months (0.66; p = 0.020 and 0.64; p = 0.014 respectively) and for the activity domain 6 months (0.47; p = 0.036). CONCLUSION: Nocturnal avoidance of allergens using TLA provided a statistically significant and clinically relevant improvement in total AQLQ score within 3 months in patients in the GINA 4 + ACT<18 group. Questions related to sleep quality may provide the first signal of response already within a month after commencing treatment.