Increase In FEV1 Research Articles

Real-world efficacy of treatment with benralizumab, dupilumab, mepolizumab and reslizumab for severe asthma: A systematic review and meta-analysis.

BackgroundSevere asthma is a major cause of morbidity. Some patients may benefit from biological therapies. Most evaluations of these treatments are derived from randomized controlled trials (RCTs), but few patients are eligible for these trials. Studies involving more diverse groups of participants exist, but there is a lack of precise pooled estimates.ObjectiveThis systematic review aims to evaluate the real‐world efficacy of recently and nearly licensed biological therapies for severe asthma to assess the generalizability of the RCT data.MethodsClinical outcomes including exacerbation rate, oral corticosteroid usage, forced expiratory volume in 1 second (FEV1) and fractional exhaled nitric oxide (FeNO) were examined. Studies were assessed for risk of bias using the Critical Appraisal Skills Programme checklist tool. The certainty of evidence was assessed using Grading of Recommendations, Assessment, Development and Evaluations (GRADE).ResultsA total of 21 studies examining biologicals in real‐world settings were identified; they mostly focused on benralizumab and mepolizumab. The introduction of biologicals reduced the annualized exacerbation rate significantly by −3.79 (95% confidence interval [CI] −4.53, −3.04), −3.17 (95% CI −3.74, −2.59) and −6.72 (95% CI −8.47, −4.97) with benralizumab, mepolizumab and reslizumab, respectively. Likewise, improvements were observed in FEV1 (0.17 L 95% CI 0.11, 0.24) and FeNO (−14.23 ppb 95% CI −19.71, −8.75) following the treatment with mepolizumab. After treatment with benralizumab, there was an increase in FEV1 (0.21 L 95% CI 0.08, 0.34).ConclusionsThese data demonstrate that anti‐IL5 biologicals may improve the clinical outcomes of patients with severe asthma in a clinic environment with similar effect sizes to RCTs. The data were mainly retrospective and unadjusted, so estimated effect sizes may not be reliable. More data are needed to acquire accurate effect estimates in different subpopulations of patients.

Dupilumab Effective in 6–11-Year-Olds With Moderate-to-Severe Asthma

Dupilumab Effective in 6–11-Year-Olds With Moderate-to-Severe Asthma

Effects of the breath stacking technique after upper abdominal surgery: a randomized clinical trial.

ABSTRACTObjective:To evaluate the effect of the association of the breath stacking (BS) technique associated with routine physiotherapy on pulmonary function, lung volumes, maximum respiratory pressures, vital signs, peripheral oxygenation, thoracoabdominal mobility, and pain in the surgical incision in patients submitted to upper abdominal surgery during the postoperative period, as well as to analyze BS safety. Methods:This was a randomized clinical trial involving 34 patients divided into a control group (CG; n = 16), who underwent conventional physiotherapy only, and the BS group (BSG; n = 18), who underwent conventional physiotherapy and BS. Both groups performed two daily sessions from postoperative day 2 until hospital discharge. The primary outcomes were FVC and Vt. The safety of BS was assessed by the incidence of gastrointestinal, hemodynamic, and respiratory repercussions. Results:Although FVC significantly increased at hospital discharge in both groups, the effect was greater on the BSG. Significant increases in FEV1, FEV1/FVC ratio, PEF, and FEF25-75% occurred only in the BSG. There were also significant increases in Ve and Vt in the BSG, but not when compared with the CG values at discharge. MIP and MEP significantly increased in both groups, with a greater effect on the BSG. There was a significant decrease in RR, as well as a significant increase in SpO2 only in the BSG. SpO2 acutely increased after BS; however, no changes were observed in the degree of dyspnea, vital signs, or signs of respiratory distress, and no gastrointestinal and hemodynamic repercussions were observed. Conclusions:BS has proven to be safe and effective for recovering pulmonary function; improving lung volumes, maximum respiratory pressures, and peripheral oxygenation; and reducing respiratory work during the postoperative period after upper abdominal surgery.

Elexacaftor/Tezacaftor/Ivacaftor in Patients with Cystic Fibrosis Homozygous for the F508del Mutation and Advanced Lung Disease: A 48-Week Observational Study.

Background: Elexacaftor/tezacaftor/ivacaftor (ETI) is the newest cystic fibrosis transmembrane conductance regulator (CFTR) modulator drug approved for the treatment of patients with cystic fibrosis (pwCF) aged ≥6 years with at least one copy of the F508del mutation (F) in the CFTR gene or another mutation that is responsive to treatment with ETI. This study determined the effectiveness and safety of ETI in a cohort of severely affected pwCF with an F/F genotype. Methods: Retrospective observational study in F/F pwCF treated for 48 weeks, enrolled in an ETI managed access program available to subjects with advanced lung disease (ppFEV1 < 40). Twenty-six patients from three centres were included. The main outcomes included lung function, sweat chloride concentration (SCC), nutrition, frequency of pulmonary exacerbations (PEx), CFQ-R, and safety. Results: ppFEV1 improved by 12.06 (95%CI 8.54, 15.57) from baseline after 4 weeks of treatment with ETI, 15.32 (11.3, 19.34) after 24 weeks, and 14.48 (10.64, 18.32) after 48 weeks. The increase in FEV1 was accompanied by a decrease in SCC, improvement of BMI, and noticeable reduction in PEx. An overall good safety profile was observed. Conclusions: In F/F pwCF with advanced lung disease with an F/F genotype, ETI was safe and associated with clinical improvement.

Pulmonary function testing for the diagnosis of asthma in preschool children.

To highlight the recent evidence of the lung function techniques used in preschool children to diagnose asthma. Several techniques are available to measure lung function and airway inflammation in preschool children, including spirometry (from age 5 years), impulse oscillometry (>3 years), whole-body plethysmography (>3 years), fractional exhaled nitric oxide (FeNO) (>5 years), multiple breath washout (>3 years), structured light plethysmography (>1-2 years) and impedance pneumography (>1 years). If applicable, measuring forced expiratory volume in 1 s (FEV1) and FEV1/forced vital capacity (FVC) ratio using spirometry is useful (cut-off < 80% predicted or below lower limit of normal [LLN] defined as z-score < -1.64) for diagnosing preschool asthma. For those unable to perform spirometry, whole-body plethysmography (sRaw > 1.6 kPa/s) and impulse oscillometry (Rrs and Xrs at 5 Hz z-score > 2) may be useful. Adding a bronchodilator reversibility test (FEV1 increase > 12%, sRaw decrease > 25-30%, Rrs at 5 Hz decrease > 40%) or a bronchial challenge test, for example, exercise test (FEV1 decrease > 10%), may improve the sensitivity of these tests. Elevated FeNO (>25-35 ppb) is a promising adjunctive test for diagnosing preschool asthma. With trained personnel, lung function testing can be done with high reliability even in children between 2 and 4 years of age. To avoid over and undertreatment of asthma, objective measurement of lung function is clinically important in preschool children.

Clinical and Lung Function Outcomes After Anti-IgE or Anti-IL5 Therapy in Severe Asthma.

BackgroundAlthough there have been indirect comparisons of the relative efficacy of mepolizumab (anti-IL-5) and benralizumab (anti-IL-5Rα) in severe asthma patients, long-term direct head-to-head comparisons are lacking. Here, we (i) examined the effect of mepolizumab, benralizumab, and omalizumab on symptom control and lung function parameters over time; and (ii) compared the efficacy of mepolizumab and benralizumab on symptom control and lung function outcomes.MethodsThis was a retrospective study of patients with severe asthma taking anti-IgE (omalizumab; n = 24), anti-IL5 (mepolizumab, n = 23), or anti-IL-Rα (benralizumab; n = 12) therapy. Data were extracted on (i) Asthma Control Questionnaire (ACQ-5) scores; (ii) forced expiratory volume over 1 second (FEV1); and (iii) peak expiratory flow rate (PEFR) at 4–6 months and 1 year and documented reductions in exacerbations. Clinical and lung function outcomes were compared between patients taking mepolizumab and benralizumab and over time.ResultsThere were significant decreases in ACQ-5 scores (3.3 ± 0.93 to 1.7 ± 0.98 for mepolizumab, 3.5 ± 0.72 to 1.6 ±0.89 for benralizumab, and 3.5 ± 0.95 to 1.7 ± 1.1 for omalizumab; t-test, all p < 0.0001) but not increases in FEV1 and PEFR for all three agents after 4–6 months of therapy, which persisted but did not decrease further at one year. There were trends toward a greater percentage increase in FEV1 and PEFR from baseline and a decrease in the number of exacerbations in patients taking benralizumab than those taking mepolizumab.ConclusionAlthough limited by a small sample size, this real-world, head-to-head comparison of mepolizumab and benralizumab is consistent with comparative data on asthma biologicals and indirect comparisons showing no major difference in efficacy. The study also generates new testable hypotheses about the efficacy of asthma biologicals in different patient populations.

Alcohol intake, beverage type, and lung function: a multicohort study of Chinese adults.

We aimed to investigate whether alcohol intake contributes to lung function levels and which beverage type may have an effect. We investigated 3742 participants from the Wuhai-Zhuhai Cohort and 12,526 participants from the Dongfeng-Tongji Cohort, and they were followed up for 3 and 5 years, respectively. Information on the type and daily amount of alcohol intake was collected through face-to-face interviews. Lung function was measured by trained physicians using electronic spirometers. Compared with nondrinkers, moderate alcohol intake was significantly associated with a 70.03 and 74.92 mL increase in FEV1 and FVC, respectively (P < 0.05), after adjusting for covariates. With regard to beverage type, red wine was associated with a 105.31 and 98.91 mL increase in FEV1 and FVC, respectively (P < 0.05). Moderate alcohol intake was also associated with a 53.37 and 66.17 mL increase in FEV1 and FVC for liquor, respectively, and a 106.90 and 103.62 mL increase for red wine (all Ps < 0.05). In the longitudinal analyses, moderate alcohol intake and red wine were associated with a 67.77 and 103.77 mL increase in FVC, respectively (P < 0.05). Moderate alcohol intake is associated with increased lung function, especially for red wine. Further studies are needed to investigate the potential mechanism.

Assessing the Utility of an Outpatient Exercise Program for Children With Cystic Fibrosis: A Quality Improvement Project.

Children with cystic fibrosis (CF) (cwCF) suffer from inadequate weight gain, failure to thrive, and muscle weakness. The latter may be secondary to disuse atrophy (muscle wasting or reduction in muscle size associated with reduced physical activity and inflammation). Handgrip strength (HGS) is a reliable surrogate for muscle strength and lean body mass. Data from our CF center have shown an association between low HGS and forced expiratory volume in 1 s (FEV1) in cwCF. High-intensity interval training (HIIT) improves physical strength. Therefore, we devised a project to assess implementing a HIIT exercise program in the home setting, in order to improve physical strength in cwCF with HGS ≤ 50th percentile. Patients were instructed to complete 3–5 sessions of HIIT exercises per week. Wilcoxon matched-pairs signed-rank tests were used to compare HGS, FEV1, and body mass index (BMI) percentile at baseline and at a follow-up clinic visit. Follow-up was limited due to the COVID pandemic. Adherence to the HIIT regimen was poor. A total of twenty-nine cwCF participated in the program. However, a total of 13 individuals reported some form of moderate activity at follow-up and therefore constituted our final study population. There was a statistically significant increase in absolute grip strength (AGS) and FEV1 for these individuals. Even though the home HIIT protocol was not followed, the project demonstrated that moderate physical activity in cwCF can lead to significant improvement in HGS and overall physical strength.

Change in individual chronic obstructive pulmonary disease assessment test item scores after short-term bronchodilator therapy and its impact on exacerbation in treatment-naïve patients with chronic obstructive pulmonary disease.

Background:The chronic obstructive pulmonary disease (COPD) assessment test (CAT) measures the health status of patients with COPD. We aimed to investigate the change in individual CAT scores after short-term bronchodilator therapy among treatment-naïve patients with COPD.Methods:Data from 148 patients newly diagnosed with COPD between January 2016 and April 2020 were retrospectively analyzed. We compared the CAT score, modified Medical Research Council (mMRC) dyspnea grade, and forced expiratory volume in 1 s (FEV1) before and after short-term (6 ± 2 months) bronchodilator therapy. We analyzed the change trends using generalized estimating equations.Results:The mean patient age was 70.9 years, and 92.6% were male. The total CAT score did not significantly improve. However, among the CAT items, phlegm [adjusted difference: –0.22 (–0.48, –0.002)], chest tightness [–0.30 (–0.56, –0.05)], and breathlessness [–0.45 (–0.66, –0.23)] scores significantly improved after bronchodilator therapy. The patients were divided into two groups: CAT score improved (n = 69) and not improved group (n = 79). The development of moderate-to-severe exacerbations during follow-up was significantly lower (2.9% versus 17.7%, p = 0.004) in the CAT score improved group.Conclusion:The improvement in CAT items indicating respiratory symptoms was more evident than the CAT total score after short-term bronchodilator therapy. Despite the significant increase in FEV1 after bronchodilator therapy, fewer than half of the patients achieved meaningful improvement in CAT, and this group showed significantly lower development of exacerbation during follow-up.

Glucocorticoid regulation of clinical and functional manifestations of asthma in patients with different airway response to hyposmolar stimulus during anti-inflammatory therapy

Introduction. The role of an alternative adenylate cyclase pathway of hormonal signal transmission under the action of synthetic glucocorticosteroids with the participation of endogenous stress-limiting activity of the adrenal cortex in conjunction with the adaptive capabilities of airway homeostasis in patients with asthma under conditions of osmotic stress has not been studied at present. Aim. To assess the dynamics of cortisol and cyclic adenosin monophosphate (cAMP) in asthma patients with different airway responses to hypoosmolar stimuli when using anti-inflammatory combination therapy with inhaled corticosteroids/long-acting β2 -agonists (ICS/LABA). Materials and methods. 96 patients diagnosed with asthma received combined anti-inflammatory therapy with ICS/LABA for 24 weeks. Group 1 included patients (n=18) with airway hyperresponsiveness to hypoosmolar stimulus, group 2 (n=78) – with no reaction of the bronchi to a 3-minute ultrasonic inhalation of distilled water. At baseline and at the end of treatment, the lung function was studied; to assess the regulatory function of glucocorticoids using non-genomic signaling pathways, the levels of cortisol in blood serum and cAMP in blood leukocytes were determined. Results. Patients of group 1 in comparison with the second one initially had a lower FEV1 ‒ 88.2±5.3 and 98.5±1.7%, respectively (p&lt;0.05), after treatment in both groups there was a slight tendency to an increase in FEV1 (98.5±5.7 and 101.4±2.5%, respectively, p&gt;0.05). The concentration of cortisol and cAMP at baseline and after 24 weeks of therapy in patients of group 1 was 588.7±32.0 and 495.0±48.7 nmol/L, 61.7±5.1 and 76.5±5, 2 pmol/106 cells (p&lt;0.01); in group 2 − 610.5±20.1 and 522.2±15.60 nmol/L (p&lt;0.001), 76.2±2.2 and 90.6±2.5 pmol/106 cells (p&lt;0.001). Conclusion. In asthma patients with airway osmotic hyperresponsiveness, persistent adaptation to osmotic stress is traced, which is combined with a more significant impairment of the lung function and indicates insufficient therapeutic control over glucocorticoid regulation of osmotic stress by the selected volume of ICS/LABA therapy.

Lung Function and Dementia Risk in the Atherosclerosis Risk in Communities (ARIC) Study

Poor lung function has been linked with adverse neurocognitive outcomes including dementia, but evidence from well-designed prospective studies is limited. We therefore examined the association between lung function, as measured by forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC), and dementia risk in 12,688 participants of the ARIC study, a prospective study of adults aged 46-70 years (at index visit, mean age =57y, 45% male, 76% White) from four US communities. Lung function was assessed in 1991-1992 (index visit, 76% normal, 16% obstructive, and 8% restrictive lung function), and dementia was ascertained through 2019 via in-person assessments, telephone interviews, and medical record surveillance, with adjudication of dementia with all in-person exams. A total of 2452 developed dementia over 30 years of follow-up. We used Cox proportional hazards model to estimate hazard ratio (HR) and 95% confidence intervals (CI), adjusting for potential confounders (socio-demographics, behavioral factors, cardiovascular risk factors, APOE ε4). Higher FEV1 and FVC were associated with reduced dementia risk [(HR: 0.86, 95%CI: 0.78-0.98, per 1L increase in FEV1) and (HR: 0.86, 95%CI: 0.80-0.93 per 1L increase in FVC)]. Compared to normal lung function, restrictive disease was associated with elevated dementia risk [(HR: 1.19, 95%CI: 1.01-1.41), n=168 dementia cases]; HR for obstructive disease, though modestly elevated (1.09, 95%CI: 0.96-1.24, n=713 dementia cases), was not statistically significant. Our findings of decreased dementia risk with better lung function may have important implications in reducing burden of dementia that is attributable to environmental exposures and associated lung function impairment.

Ruxolitinib for Bronchiolitis Obliterans Syndrome after Allogeneic Hematopoietic Stem Cell Transplantation

Introduction: Bronchiolitis obliterans syndrome (BOS) is an extremely unfavorable chronic GVHD manifestation with limited therapeutic options. Recent small retrospective series and the only prospective randomized trial have demonstrated different response rates (8.6 - 66.7%) in patients with BOS to JAK1/2 inhibitor ruxolitinib (Streiler C. et al. BMT 2020, Zhao Y. et al. Front. Pharmacol. 2021, Zeiser R. et al. NEJM 2021). Here we report a single-center study of the ruxolitinib efficacy for BOS in adults after HSCT.Methods: The study included 52 patients (median age 33 years (18-58), female 48%) diagnosed with BOS according to the NIH (2014) criteria between 2008 and 2020. The median %FEV1 at BOS diagnosis was 41.6% (20.0-74.1). Severe BOS was present in 44% patients. Due to the previous extrapulmonary cGVHD, the vast majority of patients (81%) had a history of various treatment options, including calcineurin inhibitors, systemic steroids, extracorporeal photopheresis (ECP), tyrosine kinase inhibitors (TKIs imatinib, dasatinib) and ruxolitinib. After BOS diagnosis the following treatments were administered: a FAM-like regimen (fluticasone, azithromycin and montelukast) (94%), CNIs (50%), mTOR inhibitor (35%), systemic corticosteroids (52%), ECP (25%) or low-dose rIL-2 (19%) as the first and subsequent lines of therapy. Seventeen patients (33%) received TKIs. A total of 20 BOS patients received ruxolitinib (median dose of 15 mg/day). The remaining 32 patients were included in the control group.The response was assessed by the dynamics of FEV1 according to the NIH scale (2014): partial response (PR, ≥10% increase in FEV1), stabilization (<10% change), progression (≥10% decrease) (n=45), as well as clinically by the degree of dyspnea according to the NIH symptom-based lung score and mMRC scale with PR defined as a decrease in dyspnea by at least 1 point (n=52). The overall survival (OS) was assessed with the Kaplan-Meier method from the moment of BOS diagnosis.Results: At a median follow up of 27 months (5-102) in the ruxolitinib group, 5 (26%) patients achieved PR criteria, while BOS stabilization and progression was observed in 7 (37%) cases each. In the control group, PR, stabilization and progression were documented in 3 (12%, p=0.253), 17 (65%) and 6 (23%) cases respectively (Fig.1). The clinical evaluation of dyspnea also did not reveal statistically significant differences in PR rate: 15% vs 19% according to NIH-CC and 30% vs 31% according to mMRC scale (p = 1.0). Systemic steroids were used less frequently in the ruxolitinib group (35% versus 63%, p = 0.049). As of July 1, 2021, 32 (62%) patients were alive. Twenty patients died due to cGVHD and infectious complications (n = 16, 80%) or underlying disease relapse (n = 4, 20%). As a result, the 5-year OS was 54.4% (95% CI, 36.7-69.1) with no statistically significant differences between ruxolitinib and control groups: 59.1% (95% CI, 25.6-81.6) vs 50.2 (95% CI, 29.5-67.7) (p=0.387).Conclusions: In comparison with the retrospective control group, ruxolitinib showed no significant benefit in FEV1-based and clinical response rate in patients with BOS after HSCT. However, ruxolitinib therapy provides a more frequent systemic steroid-free strategy. These data are consistent with the results of REACH3 (Zeiser R. et al. NEJM 2021). Despite very positive results of ruxolitinib in the general cGVHD population, BOS remains an unsolved problem. Novel approaches are required. [Display omitted] DisclosuresNo relevant conflicts of interest to declare. OffLabel Disclosure:Ruxolitinib for BOS in the settings of cGVHD

P9‐30: Increase in fev1 after dupilumab treatment for refractory asthma is associated with post‐treatment eosinophilia

P9‐30: Increase in fev1 after dupilumab treatment for refractory asthma is associated with post‐treatment eosinophilia

O5‐4: The effects of smoking cessation therapy on pulmonary function and predictive factor of the FEV1 increase

O5‐4: The effects of smoking cessation therapy on pulmonary function and predictive factor of the FEV1 increase

LEVEL ASSESSMENT OF CONTROL OF BRONCHIAL ASTHMA IN ADOLESCENTS

Introduction. The problem of controlling bronchial asthma in adolescents remains relevant, and its monitoring is more difficult than in other age categories, since during the period of long-term remission the disease can be accompanied by signs of bronchial hyperreactivity to nonspecific irritants, and pulmonary ventilation disorders can have a «latent» character, persisting much longer than the clinical symptoms of the disease, which leads to tactical errors in determining the level of bronchial asthma control and is a risk factor for its progression. Aim: to develop a method for assessing the level of bronchial asthma control in adolescents, when there are no clinical, anamnestic and functional signs of insufficient control of asthma, by using a quality of life questionnaire and an additional bronchodilatory test. Materials and methods. The study included 43 adolescents with mild (41.9 %) and moderate (58.1 %) controlled bronchial asthma. To identify cases of «latent» bronchospasm, a bronchodilatory test with salbutamol was performed and the increase in forced expiratory volume in 1 second (FEV1) was calculated. In the case of an increase in FEV1 ≥ 12.0 %, the presence of «latent» bronchospasm was confirmed. If the increase in FEV1 turned out to be &lt; 12.0 %, a questionnaire was performed using the Pediatric Asthma Quality of Life Questionnaire (PAQLQ) and if the value of the integral indicator of the overall quality of life PAQLQ ≤ 6.5 points, an additional bronchodilator test with a combined bronchodilator (fenoterol / ipratropium bromide). Results. The absence of changes in the initial levels of spirometric parameters was found in all 43 patients (FEV1 &gt; 80.0 %). When carrying out a bronchodilatory test with salbatamol, 7 patients (16.3 %) with a positive response (increase in FEV1 ≥ 12.0 %) were identified, which indicated cases of «latent» bronchospasm and partial control of asthma, and 36 people (83.7 %) with a negative answer (increase in FEV1 &lt; 12.0 %). Among 36 patients with an increase in FEV1 &lt; 12.0 % in the test with salbutamol applied the PAQLQ questionnaire and identified 24 people or 66.7 % with an overall quality of life of ≤ 6.5 points, which reflected the negative impact of adolescents asthma on the quality of life and lack of complete asthma control. This was confirmed in 7 out of 24 people (29.2 %) in an additional bronchodilatory test with a combined bronchodilator, in which they gave a positive response (increase in FEV1 ≥ 12.0 %; r = -0.4, p = 0.02). The reasons for the decrease in the overall quality of life of ≤ 6.5 points in the remaining 17 adolescents were due to psychoemotional states or vegetative-vascular dysfunction, and not to the latent course of «latent» bronchospasm. As a result, among 43 adolescents, 14 patients or 32.6 % with «latent» bronchospasm were found. At the same time, the relative risk of a positive patient response to a bronchodilator test with a combined bronchodilator was 2.1 times higher than during a bronchodilator test with salbutamol (OR = 2.1, 95 % CI 1.1–7.0). Conclusions. Conducting bronchodilatory tests with bronchodilators of various pharmacological groups and questioning patients using the PAQLQ questionnaire on the quality of life makes it possible to establish cases of «latent» bronchospasm even with a negative response to salbutamol, when there are no clinical and anamnestic signs of insufficient asthma control and the FEV1 index exceeds 80.0 % of proper values. Keywords: adolescents, bronchial asthma, control, bronchospasm.

The effectiveness of benralizumab in the treatment of the eosinophilic phenotype of severe asthma in real clinical practice

To evaluate the effectiveness of benralizumab in patients with the eosinophilic phenotype of severe asthma in real clinical practice after a year of therapy.Methods. During Benralizumab therapy, 13 patients with severe eosinophilic asthma (average age – 55.44 ± 7.18 years old) were examined twice: before the treatment and after 1 year of benralizumab therapy. The assessment included collection of complaints, medical history, current therapy, Asthma Control Questionnaire (ACQ-5) test, absolute blood count of eosinophils, spirometry.Results. All patients initially had pronounced eosinophilia of 577.5 ± 356.4 cells/μl. After 1 year of using benralizumab, the eosinophil count decreased by 96.15%. During therapy, the ACQ-5 index decreased from 1.63 ± 0.62 to 0.73 ± 0.41 in the study patients, which corresponded to the achievement of asthma control. The forced expiratory volume in 1 second (FEV1) increased by 23 %. The number of exacerbations decreased by 58.09%. 12 (92.31%) patients were on oral corticosteroids (OCS) (10 ± 2.17 mg of prednisolone daily) before benralizumab therapy. All subjects noted a decrease in night and day symptoms over time and were able to reduce the use of OCS. 5 (38.46%) patients achieved complete elimination of daily OCS use, 7 (53.84%) patients were able to reduce their daily OCS dose.Conclusion. Benralizumab therapy as an add-on maintenance treatment in patients with eosinophilic phenotype of severe asthma contributes to a significant decrease in peripheral blood eosinophils, which mediates an improvement in asthma control, an increase in FEV1, a reduction in the number of exacerbations, and a decrease in the need for the OCS usage. Careful monitoring of long-term adverse events is necessary during treatment with benralizumab.

Underdiagnosis of obstructive lung disease: findings from the French CONSTANCES cohort

BackgroundThe burden of undiagnosed obstructive lung disease (OLD) (mainly asthma and chronic obstructive pulmonary disease) is not fully established, and targets for corrective action are yet to be identified. We assessed the underdiagnosis of OLD and its determinants in France.MethodsCONSTANCES is a French population-based cohort of adults aged 18–69 years at inception. We analysed data collected at inclusion in 2013–2014. Undiagnosed OLD was defined as spirometry-confirmed airflow limitation (FEV1/FVC < lower limit of normal) without prior diagnosis of asthma, chronic obstructive pulmonary disease, or bronchiectasis. Multivariate analysis was performed with weighted robust Poisson regression models to estimate the adjusted prevalence ratios (aPR) of undiagnosed OLD.ResultsSpirometry results were available for 19,398 participants. The prevalence of airflow limitation was 4.6%. Overall, 64.4% of adults with airflow limitation did not report a previous diagnosis of OLD. Individuals with high cumulative tobacco consumption (≥ 10 pack-years) (aPR: 1.72 [1.28–2.32]), without respiratory symptoms (aPR: 1.51 [1.28–1.78]), and with preserved lung function (aPR: 1.21 [1.04–1.41] for a 10-point increase in FEV1% predicted) had a higher risk of being undiagnosed. Half of symptomatic individuals with airflow limitation (45% of those with moderate to severe airflow limitation) were undiagnosed with OLD.ConclusionUnderdiagnosis of OLD is very common among French adults, even in patients with respiratory symptoms. Efforts should be made in France to raise awareness about OLD in the general population, improve the detection of respiratory symptoms, and increase the use of spirometry among primary care professionals.

Changes in lung function in European adults born between 1884 and 1996 and implications for the diagnosis of lung disease: a cross-sectional analysis of ten population-based studies

During the past century, socioeconomic and scientific advances have resulted in changes in the health and physique of European populations. Accompanying improvements in lung function, if unrecognised, could result in the misclassification of lung function measurements and misdiagnosis of lung diseases. We therefore investigated changes in population lung function with birth year across the past century, accounting for increasing population height, and examined how such changes might influence the interpretation of lung function measurements. In our analyses of cross-sectional data from ten European population-based studies, we included individuals aged 20-94 years who were born between 1884 and 1996, regardless of previous respiratory diagnoses or symptoms. FEV1, forced vital capacity (FVC), height, weight, and smoking behaviour were measured between 1965 and 2016. We used meta-regression to investigate how FEV1 and FVC (adjusting for age, study, height, sex, smoking status, smoking pack-years, and weight) and the FEV1/FVC ratio (adjusting for age, study, sex, and smoking status) changed with birth year. Using estimates from these models, we graphically explored how mean lung function values would be expected to progressively deviate from predicted values. To substantiate our findings, we used linear regression to investigate how the FEV1 and FVC values predicted by 32 reference equations published between 1961 and 2015 changed with estimated birth year. Across the ten included studies, we included 243 465 European participants (mean age 51·4 years, 95% CI 51·4-51·5) in our analysis, of whom 136 275 (56·0%) were female and 107 190 (44·0%) were male. After full adjustment, FEV1 increased by 4·8 mL/birth year (95% CI 2·6-7·0; p<0·0001) and FVC increased by 8·8 mL/birth year (5·7-12·0; p<0·0001). Birth year-related increases in the FEV1 and FVC values predicted by published reference equations corroborated these findings. This height-independent increase in FEV1 and FVC across the last century will have caused mean population values to progressively exceed previously predicted values. However, the population mean adjusted FEV1/FVC ratio decreased by 0·11 per 100 birth years (95% CI 0·09-0·14; p<0·0001). If current diagnostic criteria remain unchanged, the identified shifts in European values will allow the easier fulfilment of diagnostic criteria for lung diseases such as chronic obstructive pulmonary disease, but the systematic underestimation of lung disease severity. The European Respiratory Society, AstraZeneca, Chiesi Farmaceutici, GlaxoSmithKline, Menarini, and Sanofi-Genzyme.

Real world effectiveness of benralizumab on respiratory function and asthma control.

BackgroundBiological drugs have been recognized as a breakthrough in the treatment of severe refractory asthma. This retrospective real-life observational study aims to evaluate the effect of add-on benralizumab on lung function, exacerbation rate, oral corticosteroids (OCS) reduction and asthma control questionnaire (ACQ) score after 52-weeks.MethodsIn this observational study, a cohort of 18 patients with severe eosinophilic asthma (SEA) according to the ERS / ATS and GINA 2020 classifications, with reference to the Pulmonology Unit of the Azienda USL - IRCCS, Reggio Emilia, Italy, were enrolled from 1 September 2019 to 31 August 2020. For each patient, the following data were collected: demographic data (age, sex, age of onset of asthma, history of smoking and atopy); comorbidity; clinical data (lung function, exacerbations, emergency room visits and hospitalizations); asthma control questionnaire (ACQ); biomarkers (blood eosinophil count and total serum IgE); asthma control drugs as high-dose inhaled corticosteroids / long-acting beta-adrenoceptor agonists (ICS / LABA), long-acting muscarinic antagonists (LAMA), leukotriene receptor antagonists (LTRA), theophylline, OCS. The benralizumab 30 mg treatment schedule was based on the currently recommended dosing regimen.ResultsAfter end-of-treatment (EOT), a complete weaning of all patients from OCS was confirmed. After 26 weeks, the number of exacerbations decreased from 2.90 to 0.05 (p<0.0001), hospitalizations and ACQ score decreased from 3.37 to 0.97 (p<0.0001). At EOT, the number of exacerbations was unchanged, while no hospitalizations had occurred. Overall, lung function markedly improved over the study period. After 52 weeks, the increase in FEV1 from baseline was 26,8% (p=0.0002). The subset of patients with nasal polyposis (NP) had an increase of nearly 50% (1008 ml) and patients with blood eosinophils count (BEC) greater than 500 cells / μl showed an increase of 68% (1081 ml) in FEV1 at EOT.ConclusionsThe notable improvement in respiratory function is a significant result in this study and it is much higher than what has emerged to date. This result, together with the OCS sparing effect and the excellent clinical control of asthma, makes benralizumab a reliable and safe therapeutic option for SEA.

Impact of 27Gln\Glu Polymorphisms of β2-Adrenergic Receptor Gene on Pulmonary Function in Asthmatic Children Treated with Nebulized Salbutamol

Background: The β2-adrenergic receptor gene is a typical candidate for the study of genetic polymorphism. Many patients with asthma do not respond to β2-agonist; in addition, a wide interindividual variability in pharmacological response exists, likely because of the interaction between clinical, environmental, and genetic factors. Methods: A total of 80 children (55 boys and 25 girls) with mild-moderate acute asthma attacks, ages range between 5 and 18 years, attended the Asthma Clinic at Karbala Teaching Hospital for Children were included in this study. Spirometry (Spirolab III) was used for lung function assessment before and after treatment with nebulized salbutamol, and allele-specific polymerase chain reaction was performed to determine single nucleotide polymorphisms (SNP) of β2-adrenergic receptor gene at nucleic acid 79 (27 amino acid position). Results: The effect of treatment with nebulized salbutamol on lung function in asthmatic children having different genotypes of 27Gln\Glu SNP demonstrated that patients having GG and CG genotypes showed significant improvement (P &lt; 0.05) in forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), FEV1/FVC ratio, and FEV1% predicted after treatment, while patients having CC genotype showed significant improvement (P &lt; 0.05) in FEV1, FVC, and FEV1% predicted after treatment with nebulized salbutamol without significant improvement in FEV1/FVC ratio. Patients having CG genotype of 27Gln\Glu SNP showed highest change (increase) in FEV1 (185.38 ± 174.93 ml) and in FEV1% predicted (14.96 ± 15.45%) after treatment with nebulized salbutamol in comparison with other genotype groups although this change was not statistically significant between groups. Conclusion: Asthmatic children having CG and GG genotypes of β2-adrenergic receptor gene (27Gln\Glu) showed better improvement in lung function after treatment with nebulized salbutamol in comparison with those having CC (27Gln\Glu) genotype during mild-to-moderate acute asthma attacks.