Increase In FEV1 Research Articles

Clinical predictors of treatment response to tiotropium add-on therapy in adult asthmatic patients: From multicenter real-world cohort data in Korea

BackgroundTiotropium, a long-acting muscarinic antagonist, is recommended for add-on therapy to inhaled corticosteroids (ICS)-long-acting beta 2 agonists (LABA) for severe asthma. However, real-world studies on the predictors of response to tiotropium are limited. We investigated the real-world use of tiotropium in asthmatic adult patients in Korea and we identified predictors of positive response to tiotropium add-on. MethodsWe performed a multicenter, retrospective, cohort study using data from the Cohort for Reality and Evolution of Adult Asthma in Korea (COREA). We enrolled asthmatic participants who took ICS-LABA with at least 2 consecutive lung function tests at 3-month intervals. We compared tiotropium users and non-users, as well as tiotropium responders and non-responders to predict positive responses to tiotropium, defined as 1) increase in forced expiratory volume in 1 s (FEV1) ≥ 10% or 100 mL; and 2) increase in asthma control test (ACT) score ≥3 after 3 months of treatment. ResultsThe study included 413 tiotropium users and 1756 tiotropium non-users. Tiotropium users had low baseline lung function and high exacerbation rate, suggesting more severe asthma. Clinical predictors for positive response to tiotropium add-on were 1) positive bronchodilator response (BDR) [odds ratio (OR) = 6.8, 95% confidence interval (CI): 1.6–47.4, P = 0.021] for FEV1 responders; 2) doctor-diagnosed asthma-chronic obstructive pulmonary disease overlap (ACO) [OR = 12.6, 95% CI: 1.8–161.5, P = 0.024], and 3) initial ACT score <20 [OR = 24.1, 95% CI: 5.45–158.8, P < 0.001] for ACT responders. FEV1 responders also showed a longer exacerbation-free period than those with no FEV1 increase (P = 0.014), yielding a hazard ratio for the first asthma exacerbation of 0.5 (95% CI: 0.3–0.9, P = 0.016). ConclusionsThe results of this study suggest that tiotropium add-on for uncontrolled asthma with ICS-LABA would be more effective in patients with positive BDR or ACO. Additionally, an increase in FEV1 following tiotropium may predict a lower risk of asthma exacerbation.

Dupilumab Efficacy and Safety as an Add-On Therapy in Uncontrolled Asthma Patients: A Systematic Review

Asthma is a heterogeneous chronic inflammatory condition affecting the lung. Standard treatment, a high-dose inhaled corticosteroid (ICS) and long-acting bronchodilator (LABA), effectively manages asthma in most individuals. However, 5%-10% of individuals with asthma were ineffective with those treatments. Recent RCTs suggested that Dupilumab posed potential as an add-on therapy. This systematic review aims to support the efficacy (the annualized rate of severe asthma exacerbation and increase in FEV1) and the safety of Dupilumab as an add-on therapy in uncontrolled asthma patients. We used "(Asthma) AND (Dupilumab)" as keywords on PubMed and ScienceDirect. We included only RCT design studies comparing the efficacy and safety of Dupilumab with a placebo in uncontrolled asthma patients. The placebo was ICS and LABA or oral glucocorticoids. This paper included five RCTs with 3400 participants, and their quality was assessed using Critical Appraisal Tools Program (CASP) tools. We conducted a meta-analysis to calculate the pooled risk ratio (RR). In addition, we used Mantel-Haenszel with 95% confidence intervals for dichotomous data. Furthermore, we used a random-effects model to count for interstudy heterogeneity. Then, we processed data using Revman 5.4. Dupilumab as an add-on therapy significantly showed a consistent effect in lower the annualized rate of severe asthma exacerbation (RR= 0.46; 95% CI 0.36- 0.58; p=0.007) and increased FEV1 compared to placebo. In addition, the most common adverse effect of using Dupilumab were injection site reaction, upper respiratory tract infections, and eosinophilia. In conclusion, Dupilumab is safe and well-tolerated as moderate-to-severe uncontrolled asthma add-on therapy

FROM CVID TO AERD: ADDRESSING EPITHELIAL BARRIER DYSFUNCTION FROM NON-TYPE-2 TO HIGH-TYPE-2 AIRWAY INFLAMMATION

<h3>Introduction</h3> We describe two severe asthmatics on opposite ends of the Type 2 inflammatory spectrum. One patient with high Type 2 signature including AERD. The other with low Type 2 inflammation with CVID and infection-driven asthma. Both experienced significant improvement of upper and lower respiratory symptoms with tezepelumab. <h3>Case Description</h3> A 46-year-old male AERD patient suffered from severe asthma and nasal polyposis with anosmia. His symptoms persisted despite high-dose inhaled corticosteroid/long-acting beta₂-agonist, systemic corticosteroids, budesonide saline sinus rinses, and multiple nasal polypectomies, causing a significant impact on QoL. Three months post-tezepelumab treatment resulted in 1,000 mL increase in FEV₁. He no longer needed systemic corticosteroids or use of his rescue inhaler. Anosmia resolved and taste returned. A 14-year-old female CVID patient with low peripheral eosinophil count, low total IgE, allergen skin test negativity, and low FeNO had poorly controlled asthma despite subcutaneous immunoglobulin therapy. Three months post-tezepelumab, her spirometry values normalized for the first time in years. Her FEV₁ increased by 500 mL. After tezepelumab, she was able to resume competitive sports without symptoms, no longer required corticosteroid bursts, and rare rescue inhaler use. <h3>Discussion</h3> These cases illustrate tezepelumab's ubiquitous efficacy of treating respiratory symptoms ranging from AERD to CVID. TSLP released from epithelial barrier disruptions may be a commonality across asthma endotypes. This provides insight about the unified airway and creates exciting new possibilities for the treatment of both Type 2 and non-Type 2 respiratory diseases.

Efficiency of using a short-acting β2-agonist for the relief of acute cold bronchospasm in asthma patients with cold airway hyperresponsiveness

Excessive sensitivity of the respiratory tract to physical and chemical environmental triggers can vary for many reasons, reducing the therapy effectiveness in a patient with asthma. Aim of the study was to investigate the effectiveness of a short-acting bronchodilator in patients with asthma for the relief of acute cold bronchospasm after a test of isocapnic cold air hyperventilation (ICHV). Material and methods. In 281 (161 women; 120 men, p &gt; 0.05) asthma patients with cold airway hyperresponsiveness (CAHR), the change in airway patency (FEV1) and the efficacy of short-acting β2-agonists (SABA) after a 3-minute isocapnic hyperventilation with cold (–20 ºС) air. Results. According to clinical data, patients had persistent asthma, mean age 35 (26; 44) years, 49 % of patients smoked, ACT 16 (12; 20) points, FEV1 90.0 ± 1.0 % predicted, FEV1/VC 71.4 ± 0.6 %, the increase in FEV1 after inhalation of SABA (∆FEV1β) was 11.1 (5.1; 20.5) %. The change in FEV1 for the ICHV varied within –16 (–22.0; –12.0) %. The use of SABA after the IHCV showed different efficacy for relief of an attack of cold bronchospasm. The median value of ∆FEV1β after ICHV was 21.1 (11.6; 33.3) %, with a range of –48.6 to 108.2 %. In the general group, there was a direct relationship between the level of asthma control in terms of ACT points and the baseline FEV1 (Rs = 0.17; p = 0.007), MEF25-75 (Rs = 0.18; p = 0.008), ∆FEV1β in response to SABA (Rs = –0.17; p = 0.0104), as well as the severity of the bronchial response to the ICHV (Rs = 0.15; p = 0.014). The latter, in turn, correlated with ∆FEV1β after ICHV (Rs = –0.28; p &lt; 0.0001) after HCI. Conclusions. There is a differentiated airway response to SABA after acute cold bronchoprovocation. The results obtained can serve as an important tool for phenotyping of asthma patients with CAHR for the medication correction of сold bronchospasm.

Bronchodilator reversibility testing in long-term cough and dyspnea after Covid-19 viral infection: a trigger for asthma?

Objective: This study aims to investigate the presence of underlying chronic airway disease in individuals with chronic cough and dyspnea lasting longer than eight weeks and who had previously Coronavirus disease 2019 (COVID-19) and had no known lung disease. Methods: A total of 151 patients admitted to the respiratory diseases outpatient room with the complaint of cough and/or dyspnea that persisted for at least eight weeks following COVID-19 infection were accrued to the study. Demographic characteristics, smoking history, the severity of lung involvement on chest computed tomography in the acute phase of Covid-19 infection, and bronchodilator reversibility test results were recorded. Smoking history and forced expiratory volume in the first second (FEV1) were compared. Results: FEV1 increase ≥ 200 ml was observed in 40 (26.5%) patients. In 24 (15.9%) patients, an increase in FEV1 was found to be 200 ml and above, and the percentage of FEV1 was 12% or more. While 14 (9.3%) patients were diagnosed with asthma, 13 (8.6%) patients were diagnosed with nonreversible airflow obstruction (NRAO), and 1 (0.7%) patient was diagnosed with chronic obstructive pulmonary disease (COPD). Conclusions: COVID-19 infection may play a vital role in initiating asthma pathogenesis. It should be kept in mind that viral infection-related asthma may be the underlying cause of prolonged cough and dyspnea after COVID-19 infection.

The place of diltiazem in the treatment of patients with stable angina in concomitant bronchial asthma

Introduction. In the treatment of stable angina in patients with concomitant bronchial asthma (BA), the bronchopulmonary system may be adversely affected by a number of drugs. Diltiazem may be the drug of choice when antianginal therapy with a pulseslowing effect is required, but β-blockers are contraindicated.Aim of the study. To compare the antianginal, pulse-slowing and vasoprotective effects of the calcium antagonist (CA) diltiazem, the calcium antagonist verapamil and the cardioselective beta-adrenoblocker (BAB) bisoprolol in the treatment of stable angina (SA) patients with concomitant BA.Materials and methods. The study included 60 patients with stable angina II-III FC with concomitant mild or moderate persistent BA. The patients were divided into three groups of 20 patients depending on antianginal drugs: Group 1 received betaadrenoblocker bisoprolol, Group 2 – calcium antagonist verapamil, Group 3 – calcium antagonist diltiazem. All patients underwent cardiography (Doppler EchoCG), external respiration function (ERF), endothelium-dependent vasodilation (EDVD) study at baseline and after 2, 4, 6 weeks of treatment.Results. No negative dynamics of FEV1 was found in patients of all groups during the study of ERF after 6 weeks of treatment. There was a statistically significant increase in FEV1 after 6 weeks of treatment in group 3 patients receiving diltiazem (p = 0.032). There was a statistically significant decrease in HR in all three groups during treatment, but in group 2 the dynamics were significantly lower when treated with verapamil. Analysis of mPAP of patients showed that it decreased in all groups after 6 weeks of treatment, but significant dynamics was noted only in Group 3. EDVD test after 6 weeks of treatment revealed positive dynamics, with a statistically significant increase in the index registered in patients of groups 1 and 3.Conclusions. In treatment of patients with stable angina with mild and intermediate persistent disease without exacerbation, antianginal therapy with the calcium antagonist diltiazem has marked antianginal, pulse-slowing action, has vasoprotective effect on the small and large circulatory vessels, improves the parameters of bronchial permeability.

Assessment of extrafine beclomethasone/formoterol for the treatment of chronic obstructive pulmonary disease: A non-interventional study in a Bulgarian population

BackgroundThe beneficial effects of application of a fixed dose beclomethasone dipropionate (BDP) and formoterol fumarate (F) for the treatment of severe chronic obstructive disease (COPD) has been amply proven in well controlled clinical trials. Whether this also holds for real-world conditions and in such a heterogeneous patient population as is encountered in Bulgaria remained to be investigated. MethodsIn an observational, non-interventional study, 441 Bulgarian patients with severe COPD who were enrolled at 36 sites across the country received extrafine BDP/FF-combination therapy using the NEXThaler® DPI or the Foster® pMDI over a period of 16 weeks. At visits at the beginning, after 4 weeks and at the end of the study, alterations in lung function parameters FEV1 and FVC, disease symptoms, changes in CAT score, and patient distribution in GOLD 2017 categories A through D were assessed. ResultsA large share of the Bulgarian patients with severe COPD suffered from serious comorbidities, received additional medication, and about 2/3 were former or current smokers. Extrafine BDP/FF caused an increase in mean FEV1, FVC, a decrease of health impact as assessed by the CAT score, and a considerable shift of the share of category C and D patients towards A and B. In addition, the percentage of patients that were free of symptoms impacting everyday life such as fatigue and shortness of breath at rest increased throughout the study. A comparison of both application devices indicated that the NEXThaler® was superior in terms of lung functional aspects, as these parameters displayed a constant improvement over the observation period, whereas they plateaued at week 4 when using the pMDI. ConclusionsThe therapeutic benefits of extrafine BDP/FF known from clinical trials could also be observed in a real-world setting, even in such a heterogenous patient population as the Bulgarian. The NEXThaler® appeared to be highly efficient in this setting, opening a new choice for the lung specialist and the patient to select the one device considered most suitable and practical.

Exercise induced bronchodilation: a phenomenon more common, greater magnitude and more prolonged in older adults than in adolescents

Objective There are few studies in clinically healthy subjects describing and quantifying exercise-induced bronchodilation (EIBd). This study aimed to describe and compare the magnitude and time course changes in post-exercise forced expired volume at the first second (FEV1) in healthy adolescents, younger adults, and older adults. Methods Adolescent (n = 73, aged 10–17 years), younger adult (n = 35, aged 18–25 years), and older adult (n = 25, aged 35–66 years) subjects with normal spirometry z-scores completed a maximal cardiopulmonary exercise test using the standardized exponential exercise test protocol on a cycle ergometer performed at stable temperature and humidity. Spirometry was performed pre-exercise and at 1-, 3-, 5-, and 10-minutes post-exercise to determine the percentage change in FEV1 compared to baseline. EIBd was defined as a ≥ 5% increase in post-exercise FEV1. Results Increases in FEV1 at one-minute post-exercise were observed in the adolescents (1.3%) and young adults (6.0%) with FEV1 returning to baseline after ten minutes. Compared to the adolescents, the older adults showed significantly greater and sustained increases in FEV1 at 1-, 3-, 5-, and 10-minutes post-exercise (6.4, 4.6, 4.7, and 3.8%, p < 0.05). At 1-minute post exercise a significantly greater proportion of younger adults (54%, p < 0.01) and older adults (64%, p < 0.01) demonstrated EIBd compared to the adolescent group (15%). Conclusion Healthy older adults had a higher prevalence, greater magnitude and more prolonged EIBd compared to healthy adolescent and young adult subjects.

Exercise versus airway clearance techniques for people with cystic fibrosis.

Exercise versus airway clearance techniques for people with cystic fibrosis.

Inhaled Steroids, Sex and Emphysema Index - Clinical Parameters with Impact on the Effectiveness of Valve Implantation in Patients with Severe Emphysema.

Aims and ObjectivesMany patients with chronic obstructive lung disease suffer from emphysema. Valve implantation may be a reasonable method in patients presenting advanced emphysema and absent interlobar collateral ventilation (CV). However, other clinical parameters influencing the effectiveness of endoscopic lung volume reduction (ELVR) are not well known.MethodsCOPD patients with advanced emphysema who received valve implantation in 2016 were retrospectively analyzed. The following characteristics were collected prior to valve implantation: age, sex, body mass index, presence of allergies, use of inhaled corticosteroids (ICS), lung function parameters, diffusion capacity, 6-minute walk distance (6-MWD), blood gases, COHb, smoking history, and emphysema index (quantitative multi-detector computed tomography). Three months following valve implantation, lung function parameters, diffusion capacity, 6-MWD and blood gases were measured. In this analysis, we evaluated the impact of these variables on an increase in FEV1 and 6-MWT as well as a decrease in RV three months after valve implantation.ResultsOverall, 77 COPD patients (57% male, mean age 66, mean FEV1 32%, mean RV 259%) who underwent valve therapy were enrolled. At 3-month follow-up, patients experienced a mean FEV1 increase of 0.09 ± 0.21 L, a mean RV decrease of 0.42 ± 1.80 L and a mean improvement of 8.3 ± 57 m in the 6-MWT. Overall, ICS, sex and emphysema index had an impact on the outcome following ELVR: ICS medication was associated with inferior FEV1 outcome. The higher the emphysema index, the less the RV reduction. Sex was a predictor for change of FEV1 (%), RV (L), and 6-MWT: male patients seem to benefit less than female patients from valve implantation.ConclusionThese findings suggest that ICS, emphysema index and sex are clinical parameters that may be associated with inferior outcome following ELVR. Further studies have to confirm these results to improve patient selection and clinical outcome of ELVR.

Effect of comprehensive yoga therapy on pulmonary function among various groups with chronic obstructive pulmonary disease

Introduction and Aim: COPD is a disease with involvement of multiple organ system. Our previous study has proved yoga to be useful in improving the lung function. The current study assesses the effect of yoga on lung function with respect to age, duration of illness and severity of disease due to COPD. Materials and Methods: Thirty cases of COPD were recruited in this study. Cases were assessed for lung function, peripheral oxygen saturation and exercise tolerance by 6MWT. Patients were exposed to yoga within their capacity of feasibility, and assessed for above parameters at the end of each month for about three months. A comparison study of various parameters following yoga based on age, duration of illness and severity of disease was done applying independent t test. Variables were expressed as Mean±SD. P&lt;0.05 was considered the threshold for statistical significance. Results: there was an average increase in FEV1% by 5.2 in &lt;65 years, compared to FEVI% by11.4 in &gt;65yrs (p&lt;0.05). FEV1/FVC (%) in both the age groups showed similar response following yoga intervention (p&lt; 0.01 level). We did not get any significant results with duration of illness and severity of disease. Conclusion: Regular yoga practice improves the lung parameters and also the respiratory muscle strength. In this study, COPD patients falling under higher age groups showed more of benefit with yoga. We could not elucidate any response in lung function following yoga based on duration of illness and disease severity. Yoga practice is useful in improving lung parameters in higher age groups. Regular practice of yoga has helped patients with relief from frequent exacerbation of respiratory symptoms.

Personalized targeted therapy of moderate and severe atopic asthma in Russia

Introduction. Taking into account the prevalence of asthma and especially severe atopic asthma which requires carefully selected and expensive therapy, the appearance of the domestic biosimilar omalizumab among biological therapy drugs makes the choice of treatment for this category more affordable. The article presents the results of an observational open prospective clinical trial of the omalizumab biosimilar in severe athopic asthma patients.The purposeof this study was to evaluate the efficacy and safety of the domestic production biosimilar in the real clinical practice.Materials and methods. The study involved 10 adult patients aged 19 to 55 years with a diagnosis of moderate to severe uncontrolled persistent asthma treated with mediun to high dose ICS and second&amp;more controller (ACQ-5 ≥ 1,5, FEV1 &lt; 80% of the predicted normal value). For 26 weeks all patients received the omalizumab. The evaluation of the efficacy was provided taking into account asthma symptoms improvement the results of ACQ-5, FEV1, PEF, asthma exacerbations and the use of health resources. Results. According to the results of data analysis due to omalizumab all patients demonstrated reducing daily asthma symptoms, nocturnal awakening and night time symptom, shortness of breath and SABA using. An asthma control improvement was observed after 1 month treatment (Δ ACQ-5 1.6 [1.2; 2.4], p = 0.0002 compared to the baseline data) with a continued tendency to further increase during 6 months of the study. A statistically significant increase in FEV1 was noted (initially, FEV1 56.7% [51.25; 61.8] of the predicted; after 1 month, FEV1 67.5% [63.45; 70.6] of the predicted, p = 0.00003; after 6 months, FEV1 80.6% [80.55; 84.05] of the predicted, p &gt;&lt; 0.001). Omalizumab biosimilar used allowed to reduce the background asthma therapy. No asthma exacerbation was registered due to 26 weeks omalizumab treatment. Conclusions. Based on the results of the study, it was shown that the administration of the omalizumab biosimilar to patients with severe atopic asthma improves control over the symptoms, lung function and reduces the amount of asthma exacerbations, and has a good safety&gt;&lt; 80% of the predicted normal value). For 26 weeks all patients received the omalizumab. The evaluation of the efficacy was provided taking into account asthma symptoms improvement the results of ACQ-5, FEV1, PEF, asthma exacerbations and the use of health resources.Results. According to the results of data analysis due to omalizumab all patients demonstrated reducing daily asthma symptoms, nocturnal awakening and night time symptom, shortness of breath and SABA using. An asthma control improvement was observed after 1 month treatment (Δ ACQ-5 1.6 [1.2; 2.4], p = 0.0002 compared to the baseline data) with a continued tendency to further increase during 6 months of the study. A statistically significant increase in FEV1 was noted (initially, FEV1 56.7% [51.25; 61.8] of the predicted; after 1 month, FEV1 67.5% [63.45; 70.6] of the predicted, p = 0.00003; after 6 months, FEV1 80.6% [80.55; 84.05] of the predicted, p &lt; 0.001). Omalizumab biosimilar used allowed to reduce the background asthma therapy. No asthma exacerbation was registered due to 26 weeks omalizumab treatment.Conclusions.Based on the results of the study, it was shown that the administration of the omalizumab biosimilar to patients with severe atopic asthma improves control over the symptoms, lung function and reduces the amount of asthma exacerbations, and has a good safety.

The effectiveness of single inhaler triple therapy in patients with bronchial asthma in real clinical practice

Introduction. About 40% of patients with bronchial asthma on dual therapy with inhaled glucocorticosteroids and long-acting β2-agonists do not achieve asthma control.Aim. To evaluate the efficacy of triple therapy (fluticasone furoate, umeclidinium bromide, vilanterol) in a single inhaler in patients with bronchial asthma in real clinical practice.Material and methods. The study included 43 patients with bronchial asthma from municipal outpatients’ clinics in Ekaterinburg and the Sverdlovsk region. The clinical-functional and clinical-economic efficiency of therapy was evaluated for 6 months before and after the appointment of a triple combination (fluticasone furoate, umeclidinium bromide, vilanterol) in a single inhalerResults and discussion. Of the 43 patients, 39 patients were included in the analysis. During 6 months of triple therapy in a single inhaler, the mean ACT value increased from 13 (Q1–Q3: 12–14) to 21 points (Q1–Q3: 20–22) (p &lt; 0.001), the proportion of patients with uncontrolled asthma decreased from 100% initially to 15.4% at 6 months of therapy (p&lt; 0.001). By the 6th month of therapy, all patients refused to take systemic glucocorticosteroids (p = 0.003), there was an increase in FEV1 from 73.0% (Q1–Q2: 70.0–75.0) to 82% (Q1–Q2: 80.0–86.5) (p &lt; 0.001). The number of ambulance calls (from 0.28 ± 0.46 per 1 patient at baseline) and hospitalizations (from 0.67 ± 0.84 per 1 patient at baseline) decreased to 0 (p &gt;&lt; 0.001) after 6 months of treatment with the study drug. Savings in the management of 1 patient for 6 months on a triple therapy in a single inhaler amounted to 10523 rubles, and the prevented economic damage for 39 patients for 6 months of therapy is 410418 rubles. Conclusion. The triple therapy in a single inhaler made it possible to improve asthma control and respiratory function, stop taking systemic glucocorticosteroids, reduce the number of hospitalizations and emergency calls, while reducing direct costs per unit of efficiency.&gt;&lt; 0.001). The number of ambulance calls (from 0.28 ± 0.46 per 1 patient at baseline) and hospitalizations (from 0.67 ± 0.84 per 1 patient at baseline) decreased to 0 (p&lt; 0.001) after 6 months of treatment with the study drug. Savings in the management of 1 patient for 6 months on a triple therapy in a single inhaler amounted to 10523 rubles, and the prevented economic damage for 39 patients for 6 months of therapy is 410418 rubles.Conclusion. The triple therapy in a single inhaler made it possible to improve asthma control and respiratory function, stop taking systemic glucocorticosteroids, reduce the number of hospitalizations and emergency calls, while reducing direct costs per unit of efficiency.

Effects of Azithromycin in Lung Transplant Recipients

<h3>Purpose</h3> Current evidence for azithromycin (AZM) after lung transplantation (LuTx) covers both prophylactic use to prevent BOS and treatment after the occurrence of CLAD. We hereby report the effects of AZM in our cohort of LuTx patients. <h3>Methods</h3> This was a retrospective study including all adult patients who underwent LuTx from January 2004 to June 2019 and received long term AZM (250/500 mg p.o. 3 times a week) at any time after LuTx. Effects of AZM were evaluated with BAL analysis and pulmonary function tests. Patients were considered "responders" in case of a FEV1 increase > 10% after 3 and 6 months of treatment. <h3>Results</h3> 116 patients (out of 322 LuTx) received long term AZM after LuTx for five main reasons: 56 (48.3%) for BAL neutrophilia; 12 (10.3%) for recurrent respiratory infections; 16 (13.8%) for persistent mild acute rejection; 31 (26.7%) for CLAD onset and 1 (0.9%) as a prokinetic medication. Median FEV1 improvement in the first 3 months of treatment was 20 (-36; +80) mL/month in the whole cohort; AZM responders (85 individuals) showed a 23 (13; 86) mL/month FEV1 increase, while non responders experienced a FEV1 decline of 15 (-33; -8) mL/month. Results regarding BAL neutrophilia and survival can be found respectively in Figure 1 and 2.AZM was discontinued in 9 patients for adverse events: 4 gastrointestinal intolerance; 2 NTM isolated on sputum; 2 asymptomatic QTc lengthening; 1 malaise. <h3>Conclusion</h3> Azithromycin seems to be effective in improving lung graft function, especially in those who were administered it for BAL neutrophilia and frequent respiratory infections. In these subjects, CLAD free survival was also increased. Neutrophils count on BAL was decreased in all the cohort.

Efficacy of anti-IL-5 therapy with mepolizumab for severe bronchial asthma and concomitant inflammatory nasal diseases in real clinical practice

BACKGROUND. T2 inflammation underlies non-allergic eosinophilic severe bronchial asthma and chronic rhinosinusitis with nasal polyposis (CRSwNP). Existing targeted anti-IL-5 drugs can improve clinical and functional parameters in patients with a combination of severe asthma and CRSwNP.&#x0D; AIM: to evaluate mepolizumab efficacy in patients with non-allergic severe asthma and concomitant inflammatory nasal diseases (CIND) in real clinical practice.&#x0D; MATERIALS AND METHODS. The study was conducted without a control group, by comparing related populations (before-after analysis) and based on the Sverdlovsk regional register of adult patients with severe asthma and CIND. The primary endpoint was asthma control achievement (ACT questionnaire) and decrease in the proportion of patients with uncontrolled severe asthma. The number of asthma exacerbations, emergency calls and hospitalizations, quality of life according to AQLQ questionnaire, peripheral blood eosinophils level and respiratory function (FEV1, FVC, FEV1/FVC) were also assessed. Dynamics of nasal symptoms was assessed using SNOT22 questionnaire and visual analogue scale (VAS).&#x0D; RESULTS. During 12 months of therapy with mepolizumab, ACT increased from 9 (Q1-Q3: 7-11) to 22 points (Q1-Q3: 21-24) (p0.001). The proportion of patients with uncontrolled asthma decreased from 100% to 10% (p0.001). The number of asthma exacerbations decreased from 3.182.8 per patient per year to 0 (p0.001) and hospitalizations from 0.570.9 per patient per year to 0 (p=0.007). Quality of life according to AQLQ increased from 3.481.05 (95% CI 2.734.24) to 5.590.88 (95% CI 4.966.22) points (p0.001). The number of blood eosinophils decreased from 442 (Q1-Q3: 336-853) to 90 (Q1-Q3: 73-117) cells/l (p0.001). There was increase in FEV1 from 63.9%24.2 (95% CI 46.681.2) to 80.5%18.3 (95% CI 67.493.6) (p=0.015). There was decrease in SNOT22 questionnaire score by 33 points (from 4530 to 2215) (p=0.006) and decrease in VAS score by 5 points (from 8 (Q1-Q3: 5-8) to 3 (Q1-Q3: 3-5)) (p=0.017).&#x0D; CONCLUSIONS. According to the study results, there were asthma control improvement, asthma exacerbations decrease, quality of life improvement according to AQLQ. Statistically significant peripheral blood eosinophils decrease and respiratory function improvement were also revealed. In patients with CIND, significant improvement in nasal breathing was noted, which was confirmed by scores of SNOT22 and VAS questionnaires.

Clinical Remission in Severe Asthma: A Pooled Post Hoc Analysis of the Patient Journey with Benralizumab.

IntroductionConsensus definitions for clinical remission and super-response were recently established for severe asthma. Benralizumab is an interleukin-5 (IL-5) receptor α-directed monoclonal antibody for severe, uncontrolled asthma; efficacy and safety were demonstrated in previous pivotal phase 3 trials (SIROCCO, CALIMA, ZONDA). This analysis applied a composite remission definition to characterize individual responses to benralizumab after 6 and 12 months.MethodsIn previous phase 3 studies, eligible patients were those with severe, uncontrolled asthma receiving medium- or high-dosage inhaled corticosteroids plus long-acting β2-agonists. This post hoc analysis included patients randomized to the approved benralizumab dose and not receiving oral corticosteroids (OCS) at baseline (SIROCCO/CALIMA) or OCS ≤ 12.5 mg per day (ZONDA). Individual remission components were zero exacerbations; zero OCS use; Asthma Control Questionnaire-6 (ACQ-6) score < 1.5 or ≤ 0.75; and pre-bronchodilator forced expiratory volume in 1 s (FEV1) increase ≥ 100 mL; clinical remission incorporated zero exacerbations, zero OCS use, ACQ-6 score ≤ 0.75, and pre-bronchodilator FEV1 increase ≥ 100 mL after 6 or 12 months.ResultsOverall, 609 patients (N = 301 and N = 308) and 586 patients (N = 293 and N = 293) receiving benralizumab in SIROCCO and CALIMA were included at 6 and 12 months, respectively; 40 ZONDA patients were included after 6 months. In SIROCCO/CALIMA, similar to 6-month findings, approx. 83% and approx. 49% receiving benralizumab, and 77% and 37% on placebo achieved ≥ 2 and ≥ 3 remission components after 12 months; 14.5% (85/586) on benralizumab and 7.7% (48/620) on placebo achieved clinical remission at 12 months. Among ZONDA patients, 75% and approx. 48% on benralizumab and 35% and 20% on placebo achieved ≥ 2 and ≥ 3 remission components at 6 months, respectively; 22.5% (9/40) on benralizumab and 7.5% on placebo achieved clinical remission.ConclusionsThis analysis demonstrates clinical remission is achievable by targeting the underlying drivers of inflammation. Precision medicines can help shift treatment paradigms toward treat-to-target, with clinical remission as the ultimate therapeutic goal in severe asthma.Clinical trial registrationSIROCCO (NCT01928771); CALIMA (NCT01914757); ZONDA (NCT02075255). Dr. Andrew Menzies-Gow Discusses a Post Hoc Analysis of Clinical Remission in Severe Asthma with BenralizumabSupplementary InformationThe online version contains supplementary material available at 10.1007/s12325-022-02098-1.

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.