Improvement In FEV1 Research Articles

Effect of bronchodilator therapy on the function of external respiration and lung parenchyma in surgical treatment of patients with non-small cell lung cancer combined with chronic obstructive pulmonary disease

The purpose of the study was to compare the efficacy of regular prolonged inhalation therapy with tiotropium bromide delivered via the Respimat inhaler and short-acting bronchodilator (SAB) therapy with ipratropium bromide/fenoterol in the perioperative period in patients with non-small cell lung cancer (NSCLC) combined with chronic obstructive pulmonary disease (copd).Material and Methods. The study included 66 patients with Nsclc and copd. The patients received tiotropium bromide, 5 mcg/day (TB group) or a combination of ipratropium bromide/fenoterol 20/50 mcg/dose, 2 doses 4 times a day (SAB group) for 6 weeks before and 6 weeks after surgery. The control group consisted of patients who did not receive bronchodilators before surgery, but they received a combination of ipratropium bromide/fenoterol in the postoperative period. All patients underwent tests of pulmonary function (spirometry, body plethysmography), measurement of lung parenchyma density and emphysematous lung areas (high-resolution computed tomography).Results. After preoperative preparation with use of tB or saB, there was a significant improvement in FEV1, FVC, VC, RV, ITGV, and. RV/TLC ratio relative to baseline. In the tB and sad groups, a significant reduction in the severity of total respiratory resistance (Rtot) compared to that in the control group was observed. According to the assessment of lung density and the volume of emphysematous areas on expiration, the results in the TB group were significantly better than those in the sad and control groups. six weeks after surgery, all patients showed a significant decrease in post-FeV1, post-FVC, and post-VC relative to the preoperative values. Bronchodilator therapy resulted in the reduction in Rtot in all groups; however, better results were achieved in the TB group (86 %) compared to sad group (93 %, p=0.03) and control (101.5 %, p=0.02). After surgical treatment, a decrease in the volume of emphysematous areas on inspiration was observed: the parameters were better in the TB group than in the sad and control groups (220 cm3 versus 1025 cm3 and 1002 cm3, p<0.001 and p=0.002, respectively).Conclusion. In patients with Nsclc and copd, longterm inhaled bronchodilator therapy can significantly improve respiratory function. more beneficial results are achieved after using long-acting drugs (tiotropium bromide).

The Daily Mile: The Impact of an Elementary School-Based Exercise Program on Pulmonary Function.

Implementing a structured activity to encourage exercise in children may be a strategy with benefits. We evaluated pulmonary function in elementary school children participating in a school-based exercise program called The Daily Mile. During the fall semester, we implemented The Daily Mile program in one elementary school and compared pulmonary function in children in the intervention school pre- and postintervention to children in a control school in the same community. The primary outcomes were forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), and FEV1% (the FEV1/FVC ratio). The children in the control school showed no significant change in FEV1% during the semester (P=.06). On the other hand, children in the intervention school showed a significant improvement in FEV1% during the same semester (P=.001). This effect was consistent even when stratifying by asthma and sports participation. The Daily Mile has benefits for pulmonary function in children. Although family physicians should continue to encourage their patients to have a healthy lifestyle, a more effective approach may be to encourage schools to adopt a program that teachers oversee and administer in a structured way.

The phenotypic heterogeneity of obese and nonobese patients with severe asthma and comparison of omalizumab-mepolizumab treatment efficiency in these patients.

In obese severe asthmatics, the degree of type 2 inflammation may vary according to their atopic status and past smoking history. In this study, we aimed to analyze the clinical and physiopathological features of obese and nonobese severe asthmatics treated with omalizumab or mepolizumab treatment. In addition we aimed to compare the clinical, spirometric outcomes and total peripheral eosinophilic count (TEC) changes after treatment with these 2 biologic agents in obese and nonobese groups. In this retrospective, cross sectional study, 121 severe asthmatic treated with biologic agents (omalizumab = 88 or mepolizumab = 33) for at least 16 weeks were included. Obese (n: 44) and nonobese severe asthmatics (n: 77) were analyzed according to whether they provided a ≥ 10 pack/years (p/y) or <10 p/y smoking history and were found to be atopic. Obese and nonobese groups were compared in terms of the change in the asthma control test, asthma attacks, TEC, and forced expiratory volume in the first second (FEV1) after treatment. In patients with ≥10 p/y smoking history, nonobese group had a significantly higher TEC compared to obese group [median (min-max) 660 cells/μL (200-1500) vs 300 cells/μL (110-770); p: 0.013]. Within the nonobese group, nonatopic patients had a significantly higher TEC compared to atopic patients [median (min-max) 1200 cells/μL (100-2100) vs 310 cells/μL (0-2730); p: 0.021]. Both biologic agents had similar effects on improving asthma control test and in reducing asthma attacks; however, mepolizumab was more effective in suppressing TEC. The improvement in FEV1 in obese group following biologic 2 agents was very similar but in nonobese group, mepolizumab was found to be superior (510 mL vs. 295 mL; p: 0.034). In our real-life study, nonobese severe asthmatics with ≥10 p/y smoking history and those that were nonatopic had higher TEC. Compared to omalizumab, mepolizumab was superior at reducing TEC in all asthmatics and in improving FEV1 in nonobese group.

O028 Worsened sleep and mood after initiating elexacaftor/tezacaftor/ivacaftor treatment in children with cystic fibrosis

Abstract Background CFTR modulator Elexacaftor/tezacaftor/ivacaftor (ETI) significantly improves lung function and but its effect on mental health and sleep remains poorly understood. We report sleep, mood and respiratory health outcomes of adolescents with CF with ETI therapy. Methods We conducted a prospective longitudinal study of 31 adolescents (aged 10 to 18 years) from July 2021 to October 2022. Data collected include demographics, pediatric daytime sleepiness scale (PDSS), sleep disturbance scale for children (SDSC), patient health questionnaire-9 (PHQ-9), generalised anxiety disorder-7 (GAD-7) scores and FEV1 percent predicted. Results Paired-T testing demonstrated a significant improvement in FEV1, whereas PDSS, PHQ-9, and GAD-7 scores worsened following ETI therapy, but did not reach statistical significance. SDSC scores marginally reduced. Ten percent of participants developed new onset sleep concerns and new mood concerns developed in 10% following ETI initiation. Conclusion/Outcome This is the first prospective longitudinal study of sleep and mood changes with ETI in adolescents with CF. ETI does not improve sleep and mood in the same way as respiratory health outcomes.

Dupilumab Efficacy in Patients with Type 2 Asthma with and without Elevated Blood Neutrophils.

Elevated neutrophil counts in blood, sputum, or lung have been associated with poor clinical outcomes and more severe disease in patients with type 2 asthma. In the phase 3 LIBERTY ASTHMA QUEST (NCT02414854), add-on dupilumab 200 and 300 mg every 2 weeks compared with matched placebo significantly reduced severe asthma exacerbations and improved forced expiratory volume in 1 s (FEV1) in patients with uncontrolled, moderate-to-severe asthma. This post hoc analysis explored the efficacy of dupilumab in patients with type 2 asthma enrolled in QUEST with or without elevated blood neutrophil counts. Annualized severe exacerbation rates during the 52-week treatment period and least-squares mean change from baseline in FEV1 over time were evaluated for patients with elevated type 2 biomarkers at baseline (blood eosinophils ≥ 150 cells/µL or fractional exhaled nitric oxide (FeNO) ≥ 20 ppb; and eosinophils ≥ 300 cells/µL or FeNO ≥ 50 ppb) and low (<4,000 cells/µL) or high (≥4,000 cells/µL) neutrophil counts. Dupilumab significantly reduced annualized severe exacerbation rates compared with placebo during the 52-week treatment period in patients with elevated type 2 biomarkers, irrespective of baseline neutrophil count (P < 0.0001 for all comparisons). Significant improvements in FEV1 versus placebo were observed as early as Week 2 and over the 52-week treatment period, irrespective of baseline neutrophil count (P < 0.001 for all comparisons). Safety findings were similar across all subgroups, regardless of neutrophil counts at baseline. Dupilumab treatment significantly reduced annualized severe exacerbation rates and improved lung function in patients with uncontrolled, moderate-to-severe, type 2 asthma, irrespective of baseline blood neutrophil count. This trial is registered with NCT02414854.

Effect of Thyroidectomy on Tracheal Remodeling and Airway Physiology in Apparently Asymptomatic Patients with Goiter: A Prospective Study.

Tracheal airflow limitation is frequently reported in patients with goiter but is severely underestimated, and studies on how goiter and its treatment affect trachea are scarce. Moreover, the choice of the optimal treatment for individual patient with asymptomatic goiter is not straightforward. Therefore, in this study we aim to investigate the effect of goiter and subsequent thyroidectomy on tracheal anatomy and change in airflow in asymptomatic patient with goiter. Seventy patients undergoing total/hemithyroidectomy (TT/HT) from Feb 2020 to Feb 2021 satisfying inclusion criteria were enrolled in the study. Neck radiograph (NR) and forced spirometry (FS) were performed preoperatively and on postoperative day 10 and 6weeks and 3months. Out of 70 patients, 84.3% patients were female, and mean duration and weight of goiter were 54.7months and 72.21gm, respectively. Of 70 patients, 57 were of benign pathology. Significant improvement in tracheal compression with moderate improvement in deviation was observed after surgery. Preoperative spirometry showed significant reduction in almost all parameters. After surgery, a weak improvement was observed at postoperative day 10 and 6weeks; however, significant improvement in FEV1, PEFR, FEV1/FEV0.5, and FEF50%/FIF50% was observed at postoperative 3months. Patient with right sided and those with ≥ 8mm deviation were associated with poorer pulmonary function. Weak correlation was observed between neck NR and spirometry parameters. Weight of the thyroid gland significantly correlated with ratio of MVV/FEV1. Patients with asymptomatic goiter can have significant abnormal changes in airflow as evidenced by FS and NR. Thyroidectomy is followed by gradual restoration of tracheal deviation and compression with significant improvement in pulmonary airflow.

The effect of biologics in lung function and quality of life of patients with united airways disease: A systematic review

Increasing evidence supports the united airway disease concept for the management of upper and lower respiratory tract diseases, particularly in patients with asthma and chronic rhinosinusitis with nasal polyps (CRSwNP). However, evidence for a combined approach in asthma and CRSwNP is scarce. In this systematic review, we focused on the role of biologics in the lung function and quality of life in patients with severe asthma and CRSwNP. We conducted a systematic search of 3 electronic databases using 2 search strategies to identify studies published from January 2010 to March 2022. Quality assessment was performed with the Critical Appraisal Skills Programme. Of 1030 studies identified, 48 original studies reporting data of benralizumab (12), dupilumab (14), mepolizumab (10), omalizumab (13), and reslizumab (2) were analyzed. Primary diagnosis was mostly asthma or CRSwNP, with only 15 studies, mainly observational, performed in populations with united airway disease. In total, 18 studies reported data on quality of life (mostly 22-item Sino-Nasal Outcome Test score), 8 on lung function (mostly FEV1), and 22 on both outcomes. Significant FEV1 and 22-item Sino-Nasal Outcome Test score improvements were consistently observed after 24-week treatment, and thereafter, mostly in real-world studies that included variable proportions of patients with asthma/CRSwNP. The use of biologics in patients with severe asthma and CRSwNP was overall associated with significant improvements in lung function and quality of life. However, we observed a high heterogeneity of populations and outcome measurements across studies. Notwithstanding the need of larger studies, our results reinforce the joint management of asthma and CRSwNP as united airway disease in clinical practice.

Long-term efficacy of dupilumab in severe asthma by baseline oral corticosteroid dose.

Dupilumab has been shown to improve clinical outcomes long term while reducing oral corticosteroid (OCS) dose in patients with severe OCS-dependent asthma. This post hoc analysis assesses the impact of OCS dose at baseline (≤10 or >10 mg·day-1) on long-term outcomes of dupilumab treatment. Annualised severe asthma exacerbation rates, forced expiratory volume in 1 s (FEV1), measures of asthma control and quality of life, and OCS dose were evaluated in patients from the phase 3 VENTURE trial with severe OCS-dependent asthma, further categorised by OCS dose ≤10 or >10 mg·day-1 at parent study baseline (PSBL), who enrolled in TRAVERSE. Dupilumab reduced the annualised exacerbation rate in VENTURE, and it remained low throughout TRAVERSE (0.202-0.265 (OCS ≤10 mg·day-1 at PSBL) and 0.221-0.366 (OCS >10 mg·day-1 at PSBL)). Improvements in pre-bronchodilator FEV1, asthma control and quality of life observed in VENTURE dupilumab patients were sustained throughout TRAVERSE. Patients on placebo during VENTURE showed rapid improvements in FEV1 upon initiating dupilumab in TRAVERSE, which were sustained to the end of TRAVERSE. Reductions in OCS dose observed in VENTURE were maintained throughout TRAVERSE, with more than two-thirds of patients achieving reductions in OCS doses to ≤5 mg·day-1 by TRAVERSE week 48. Improvements in clinical outcomes and reductions in OCS dose with dupilumab observed in VENTURE were maintained throughout TRAVERSE, regardless of baseline disease severity. Patients who switched from placebo in VENTURE to dupilumab in TRAVERSE had improved clinical outcomes and reductions in OCS dose comparable to those given dupilumab in VENTURE.

Determination of sputum eosinophil count and serum absolute eosinophil count in patients with bronchial asthma and its correlation with disease severity and response to treatment.

Sputum eosinophils can be used to assess severity of disease and response to treatment in bronchial asthma. Eosinophilic inflammation in the airways can also be marked by blood eosinophilia. In this study, we tried to determine the sputum eosinophil count and serum absolute eosinophil count in patients with asthma and correlate them with disease severity and treatment response. It was a cross-sectional intervention study including all consecutive cases with a diagnosis of bronchial asthma based on spirometry and clinical history. An induced sputum sample and blood were sent for eosinophil count to the laboratory. All the patients were started on inhaled corticosteroids and followed up at the end of 1 month with spirometry, sputum eosinophil count and AEC. Statistical Package for the Social Sciences for Windows v20.0 (IBM SPSS Corp.; Armonk, NY, USA) was used for statistical analysis. There was no significant difference in the mean sputum eosinophil count (%) in mild, moderate and severe disease (f = 0.24; P = 0.79) or in AEC (f = 1.48; P = 0.24). At follow-up, all patients with moderate and severe disease showed significant improvement in FEV1 (P = 0.0001). The mean sputum eosinophil count and AEC (%) in the three subgroups was also seen to decrease at the end of the follow-up period (f = 0.08; P = 0.9 and f = 2.75; P = 0.07, respectively). Sputum eosinophils and AEC are important markers of airway inflammation. All our patients showed improvement in FEV1, sputum eosinophil count and AEC after 1 month of treatment thus confirming the role of ICS in the treatment of eosinophilic asthma.

Does NSAID exacerbated respiratory disease (N-ERD) accompanying severe asthma affect biological treatment response? Efficacy of omalizumab and mepolizumab in N-ERD

IntroductionNon-steroidal anti-inflammatory drug (NSAID)-exacerbated respiratory disease (N-ERD) accompanies severe asthma in about 15% of the patients and may adversely affect the prognosis. Omalizumab and mepolizumab are biologics used in patients with severe asthma. The objective of this study is to assess the respiratory improvements, after these biologics in severe asthmatic patients stratifed by the presence of concomitant Non-erosive reflux disease (N-ERD) and the effect of omalizumab and mepolizumab in severe asthmatics with N-ERD. Material & methodThe population of this three-center, retrospective, cross-sectional, observational study comprised patients using omalizumab or mepolizumab for severe asthma. Patients administered these biologics for severe asthma were comparatively analyzed for the presence of N-ERD; asthma control test (ACT) scores, number of attacks, and the changes in forced expiratory volume in 1 s (FEV1) were assessed. Subsequently, patients who were found to have N-ERD were analyzed using visual analog scale (VAS) in terms of the changes in their nasal parameters (ie, nasal obstruction, facial pain, anterior-posterior rhinitis, and hyposmia), according to whether they use omalizumab or mepolizumab. ResultsThe use of biologics resulted in a significant improvement in ACT and FEV1 and reduction in attacks in 28 severe asthmatics with N-ERD and 125 without N-ERD. Although both biologics resulted in a significant improvement in the respiratory parameters, omalizumab treatment resulted in a significant improvement in nasal parameters except hyposmia, mepolizumab treatment resulted in a significant improvement only in posterior rhinitis, and nasal obstruction among the nasal parameters. ConclusionThis study is the first to address both omalizumab and mepolizumab treatments in severe asthmatics with N-ERD. The improvement in nasal parameters was more pronounced in patients who were administered omalizumab. Large-scale randomized controlled studies are needed to corroborate the findings of this study.

Efficacy, Safety, and Systemic Exposure of Once-Daily Indacaterol Acetate in Pediatric Asthma: A Randomized, Double-Blind, Controlled Dose-Finding Study.

Indacaterol acetate (IND), a long-acting β2-agonist in combination with mometasone furoate (MF), an inhaled corticosteroid (ICS), is being explored as a once-daily (od) treatment for asthma in children. This study examined the efficacy, safety, and systemic exposure of IND 75 µg and IND 150 µg in children with persistent asthma. In this Phase IIb, multicenter, randomized, double-blind, parallel-group study, pediatric patients (aged ≥6 to <12 years) with persistent asthma were randomized (1:1) to receive either IND 75 µg od or IND 150 µg od via Breezhaler® in combination with ICS background therapy. The primary endpoint was change from baseline in pre-dose trough forced expiratory volume in one second (FEV1) after two weeks of treatment. In total, 80 patients received IND 75 µg (n = 39) or IND 150 µg (n = 41). The study met its primary endpoint; both doses demonstrated improvements in pre-dose trough FEV1 from baseline to Day 14 (mean change [Δ]: 212 mL, IND 75 µg; 171 mL, IND 150 µg). The secondary spirometry parameters (post-dose FEV1 after 1-h, post-dose forced vital capacity; morning and evening peak expiratory flow) also improved. Overall, 36.1% in IND 75 μg group and 25% patients in IND 150 μg group achieved a decrease from baseline in Pediatric Interviewer-administered Asthma Control Questionnaire score of ≥0.5 units. A dose-dependent increase in plasma IND concentration was noted between the two groups. Both IND doses demonstrated an acceptable safety profile. Once-daily IND 75 μg and IND 150 μg via Breezhaler® in combination with background ICS therapy provided substantial bronchodilation in children with asthma and were well tolerated. Taken together, these clinical and systemic exposure findings support IND 75 μg as the most appropriate dose for evaluation in Phase III trials in combination with MF in pediatric asthma. ClinicalTrials.gov (NCT02892019; 08-Sep-2016).

Benralizumab and mepolizumab treatment outcomes in two severe asthma clinics.

This study compared the clinical outcomes of severe asthmatics treated with mepolizumab and benralizumab in a tertiary care severe asthma service setting. Patient data at baseline, six and 12 months were collected prospectively at two large tertiary hospital severe asthma clinics following treatment initiation. Two hundred and four patients received treatment with mepolizumab (117) or benralizumab (87). Baseline characteristics between groups were similar in regard to age, gender, body mass index, steroid dose and blood eosinophil count. However, the mepolizumab cohort had a higher Asthma Control Questionnaire Score (ACQ) at baseline (4.0 ± 1.1 vs. 3.6 ± 0.9, p = 0.018), accompanied by more frequent reliever medication usage and lower prebronchodilator FEV1 % (56.0 ± 20.1 vs. 63.8 ± 18.9, p = 0.008). After 6 months treatment, both treatments induced significant improvements in (i) ACQ of 2.3 ± 0.1 (p < 0.001), (ii) oral steroid requiring exacerbations (incident rate ratio 0.26 (0.18-0.37), p < 0.001) and (iii) FEV1 . However, the improvement in FEV1 was 0.18 (0.05-0.30) litres greater with benralizumab than with mepolizumab (p = 0.002) even when adjusting statistically for baseline differences between groups. These differences were even more pronounced at 12 months post-treatment initiation, when the improvement in exacerbation frequency with benralizumab was 64% greater than with mepolizumab (p = 0.01). Whilst both treatments significantly reduced the blood eosinophil count at 6 and 12 months, this reduction was substantially greater with benralizumab than mepolizumab (-260 cells/μL [-400 to -110, p = 0.001]). In this large group of severe eosinophilic asthmatics, mepolizumab and benralizumab both improved disease parameters. However, benralizumab treatment appeared significantly more effective than mepolizumab in reducing exacerbations, improving FEV1 and depleting blood eosinophils.

Efficacy and safety of aclidinium/formoterol versus monotherapies and aclidinium versus placebo in Chinese and other Asian patients with moderate-to-severe COPD: The AVANT Phase 3 study

AVANT was a Phase 3, 24-week, randomized, parallel-group, double-blind, double-dummy, placebo-controlled study to assess the efficacy and safety of aclidinium/formoterol 400 μg/12 μg combination vs monotherapies and aclidinium vs placebo (1:1:1:1) in Asian patients (∼70% of whom were Chinese) with moderate-to-severe stable chronic obstructive pulmonary disease. Endpoints were analyzed hierarchically to incorporate type I error control. At Week 24, aclidinium/formoterol demonstrated improvements from baseline in 1-h morning post-dose forced expiratory volume in 1 s (FEV1) vs aclidinium (least squares [LS] mean 92 mL; 95% confidence interval [CI] 60, 124 mL; p < 0.001), and in trough FEV1 vs formoterol (LS mean 85 mL; 95% CI 53, 117 mL; p < 0.001). Furthermore, aclidinium provided improvements in trough FEV1 vs placebo (LS mean 134 mL; 95% CI 103, 166 mL; p < 0.001). There was an improvement in transition dyspnea index focal score at Week 24 for aclidinium/formoterol vs placebo (LS mean 0.8; 95% CI 0.2, 1.3; p = 0.005) but not for aclidinium vs placebo (LS mean 0.4; 95% CI −0.1, 1.0; p = 0.132). Improvements in St George's Respiratory Questionnaire total scores occurred for aclidinium/formoterol vs placebo (LS mean −4.0; 95% CI −6.7, −1.4; p = 0.003) and aclidinium vs placebo (LS mean −2.9; 95% CI −5.5, −0.3; p = 0.031). Aclidinium/formoterol and aclidinium were well tolerated and safety findings were consistent with known profiles; rates of treatment-emergent adverse events (AEs) (aclidinium/formoterol: 54.8%; aclidinium: 47.4%; placebo: 53.9%), serious AEs (7.2, 7.9, and 7.8%, respectively), and AEs leading to discontinuation of study medication (2.3, 1.5, and 2.2%, respectively) were similar between groups.

Health-Related Quality of Life Improves in Parallel with FEV1 and 6-Minute Walking Distance Test at Between 3 and 12 Months in Critical COVID-19 Survivors

BackgroundIn COVID-19 intensive care unit (ICU)–admitted patients, multiorgan acute complications lead to long-lasting sequelae. The aim of this study was to assess (1) changes in chest CT, pulmonary function test (PFT), functional capacity (6-minute walking distance test (6MWT)), and health-related quality of life (HR-QoL) among ICU COVID-19 survivors at 3, 6, and 12 months after ICU discharge and (2) predictors of persistent impairment/improvement in 6MWT and HR-QoL. MethodsICU COVID-19 survivors were prospectively included. Outcomes at 3, 6, and 12 months included PFT, 6MWT, respiratory muscle strength (RMS), HR-QoL (SF-36), Medical Research Council dyspnea scale (mMRC), and post-COVID Functional Status scale. ResultsEighty-seven survivors were included, from June 3, 2020, to September 2, 2021. At 12 months, 50% of PFT were normal, 46% were restrictive, and 22% showed reduced diffusing capacity for carbon monoxide (DLCO). Impaired DLCO was associated with ICU length of stay and age. In mixed linear model analysis, improvements in RMS and mMRC persisted over time regardless of the adjustments applied (P ≤ .050). SF-36 improved in parallel with FEV1 and 6MWT between 3 and 12 months (P ≤ .044), while increment in DLCO correlated with changes in FEV1 and total lung capacity (TLC) (p ≤ 0.026). ConclusionsThis longitudinal study demonstrated that improvements in SF-36 occur in parallel with improvements in FEV1 and 6MWT between 3 and 12 months post-ICU discharge in a sample of critically ill COVID-19 patients. However, PFT remained, however, abnormal in 50% of patients. Based on continued improvements observed from 3 to 12 months, it is anticipated that COVID-19 ICU patients will continue to recover similarly to ARDS patients.

Real world outcomes of CFTR modulator therapy in Australian adults and children

BackgroundRecent advances in CFTR modulator therapy have the potential to change the face of cystic fibrosis (CF). This retrospective observational study describes real world experience of the four available CFTR modulators in adults and children with CF in a single centre in Melbourne, Australia. MethodData were collected for all patients treated with CFTR modulators at MonashCF between May 2012 and September 2020. Primary outcomes included lung function, admission days and BMI/BMI centile over time. Adverse events and reasons for changing or ceasing medications were also analysed. Results55% (74/133) adult and 46% (55/119) paediatric patients were treated with CFTR modulators. FEV1 increased in adults treated with ivacaftor (IVA) and elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) by 4.73% and 10.07% respectively, and BMI also improved in these groups. Nutrition improved in adults and children treated with lumacaftor/ivacaftor (LUM/IVA). There was no significant improvement in FEV1 or admission days with LUM/IVA or tezacaftor/ivacaftor (TEZ/IVA). 36% (31/85) ceased LUM/IVA, due to adverse effects in 81% (25/31). Of these, 92% (23/25) changed to TEZ/IVA, 78% (18/23) without significant adverse effects. ConclusionsOur findings for LUM/IVA and TEZ/IVA are less encouraging than those seen in clinical trials, with no significant improvement in lung function or admission days and a higher rate of adverse effects with LUM/IVA compared with phase 3 clinical trials. TEZ/IVA was generally well tolerated by those who experienced side effects with LUM/IVA. The small number of patients treated with ELX/TEZ/IVA had improvements in all parameters. These findings support ongoing use of IVA for individuals with gating mutations, and transition to ELX/TEZ/IVA once available for patients with at least one Phe508del mutation.

Lung volume reduction for emphysema using one-way endobronchial valves: An Australian cohort.

Emphysema can be associated with gas trapping and hyperinflation, which negatively impacts on quality of life, life expectancy, and functional capacity. Lung volume reduction (LVR) surgery can reduce gas trapping and improve mortality in select patients but carries a high risk of major complications. Bronchoscopic techniques for LVR using one-way endobronchial valves (EBV) have become an established efficacious alternative to surgery. A bi-center retrospective cohort study was conducted on patients with severe emphysema who underwent endoscopic lung volume reduction (ELVR) using Pulmonx Zephyr EBVs. Symptomatic patients with gas-trapping and hyperinflation on lung function testing were selected. Target-lobe selection was based on quantitative imaging analysis and ventilation-perfusion scintigraphy. Successful procedures were determined from clinical review, imaging and follow-up testing. Thirty-nine patients underwent ELVR. Mean pre-procedure forced expiratory volume in 1 second (FEV1) was 0.75 L, residual volume (RV) was 225% predicted and total lung capacity was 129% predicted. Most common treated-lobe was left upper lobe. Post-procedure pneumothorax occurred in 36.5% of patients with 73% requiring intercostal catheter insertion for drainage. Mean FEV1 improvement was +140 mL and 57% of patients achieved minimal clinical important difference FEV1 increase of ≥12%. Maximal mean RV change was -1010 mL with 69% of patients achieving minimal clinical important difference RV decrease of ≥350 mL. Clinician-determined success of ELVR was 78%. Procedure-related mortality was absent. LVR using EBVs is safe and can lead to significant improvements in lung function, particularly reduction of gas trapping and hyperinflation. Occurrence of pneumothorax post-procedure is a complication that must be monitored for and managed appropriately.

Adolescent Asthma Monitoring: A Preliminary Study of Audio and Spirometry Modalities.

Asthma patients' sleep quality is correlated with how well their asthma symptoms are controlled. In this paper, deep learning techniques are explored to improve forecasting of forced expiratory volume in one second (FEV1) by using audio data from participants and test whether auditory sleep disturbances are correlated with poorer asthma outcomes. These are applied to a representative data set of FEV1 collected from a commercially available sprirometer and audio spectrograms collected overnight using a smartphone. A model for detecting nonverbal vocalizations including coughs, sneezes, sighs, snoring, throat clearing, sniffs, and breathing sounds was trained and used to capture nightly sleep disturbances. Our preliminary analysis found significant improvement in FEV1 forecasting when using overnight nonverbal vocalization detections as an additional feature for regression using XGBoost over using only spirometry data.Clinical relevance- This preliminary study establishes up to 30% improvement of FEV1 forecasting using features generated by deep learning techniques over only spirometry-based features.

Factors associated with lung function response with oral antibiotic treatment of pulmonary exacerbations in cystic fibrosis

Pulmonary exacerbations treated with oral antibiotics (oPEx) have a significant effect on lung function decline in people with cystic fibrosis (CF). However, factors associated with lung function response with oPExs are not well defined.We performed a retrospective cohort study of pediatric and adult patients with CF followed in the Toronto CF Database. Lung function response was measured both as the change in forced expiratory volume in 1 second (FEV1) from Day 0 of antibiotic therapy to end of treatment as well as from baseline to end of treatment. Drop from baseline to Day 0 FEV1 was strongly associated with lung function response (p<0.001). Greater FEV1 improvements were associated with longer antibiotic treatment durations. Older, female patients had less improvements in FEV1 at end of treatment compared to younger, male patients.

Dupilumab sustains efficacy in patients with moderate-to-severe type 2 asthma regardless of ICS dose.

Dupilumab, a human monoclonal antibody, blocks the shared receptor component for interleukins-4/13, key and central drivers of type 2 inflammation. The TRAVERSE (NCT02134028) open-label extension study demonstrated the long-term safety and efficacy of dupilumab in patients ≥12 years who completed a previous dupilumab asthma study. The safety profile was consistent with that observed in the parent studies. Here, we assess whether dupilumab sustains long-term efficacy in patients regardless of inhaled corticosteroid (ICS) dose at parent study baseline (PSBL). Patients from phase 2b (NCT01854047) or phase 3 (QUEST; NCT02414854) studies receiving high- or medium-dose ICS at PSBL and enrolled in TRAVERSE were included. We analyzed unadjusted annualized severe exacerbation rates, change from PSBL in pre-bronchodilator (BD) forced expiratory volume in 1 second (FEV1 ), 5-item asthma control questionnaire, and type 2 biomarkers in patients with type 2 asthma at baseline (blood eosinophils ≥150 cells/μL or fractional exhaled nitric oxide [FeNO] ≥25 ppb), and subgroups defined by baseline blood eosinophils or FeNO. Of patients with type 2 asthma (n = 1666), 891 (53.5%) were receiving high-dose ICS at PSBL. In this subgroup, unadjusted exacerbation rates for dupilumab versus placebo were 0.517 versus 1.883 (phase 2b) and 0.571 versus 1.300 (QUEST) over the parent study (52 weeks) and remained low throughout TRAVERSE (0.313-0.494). Improvements in pre-BD FEV1 were sustained throughout TRAVERSE. Similar clinical efficacy was observed among patients receiving medium-dose ICS at PSBL and biomarker subgroups. Dupilumab showed sustained efficacy for up to 3 years in patients with uncontrolled, moderate-to-severe type 2 asthma on high- or medium-dose ICS.

Severe asthma clinical remission after biologic treatment with anti-IL4/IL13: A real-life experience

IntroductionDupilumab, a fully human anti-interleukin-4/interleukin-13 monoclonal antibody, has shown efficacy in many aspects of Type-2 severe asthma management. Currently, we lack real-life studies addressing the achievment of clinical remission in patients treated with this biologic. Materials and methodsWe performed a prospective study enrolling 18 patients with severe asthma treated with Dupilumab. We assessed main clinical, functional and biological severe asthma features at baseline (T0) and after a 1-year course of treatment (T12). Clinical remission was defined at T12 in patients without asthma exacerbations, no oral corticosteroid (OCS) use, ACT ≥ 20 and FEV1 improvement ≥ 100 ml from baseline. ResultsAmong total population, 38.9% of patients achieved clinical remission at T12. Anti IL-4/IL-13 treatment significantly reduced asthma exacerbations and OCS use in the overall cohort, with a more pronounced ACT improvement in the remission group. Patients achieving clinical remission went through a step down of the inhalation therapy, suspending long-acting anti-muscarinics administration at T12. ConclusionsTreatment with anti-IL4/IL13 can induce clinical remission in patients with T2 severe asthma.