Improvement In Forced Expiratory Volume Research Articles

Endobronchial valves for emphysema and persistent air-leak: 10-year experience in an Asian country

BackgroundEndobronchial valve (EBV) therapy, a validated method for bronchoscopic lung volume reduction (BLVR) in severe emphysema, has been explored for persistent air-leak (PAL) management. However, its effectiveness and safety in the Asian population require further real-world evaluation. In this study, we assessed the outcomes of treatment with EBV within this demographic.MethodsWe conducted a retrospective analysis of medical records from 11 Korean centers. For the emphysema cohort, inclusion criteria were patients diagnosed with emphysema who underwent bronchoscopy intended for BLVR. We assessed these patients for clinical outcomes of chronic obstructive pulmonary disease. All patients with PAL who underwent treatment with EBV were included. We identified the underlying causes of PAL and evaluated clinical outcomes after the procedure.ResultsThe severe emphysema cohort comprised 192 patients with an average age of 70.3 years, and 95.8% of them were men. Ultimately, 137 underwent treatment with EBV. Three months after the procedure, the BLVR group demonstrated a significant improvement in forced expiratory volume in 1 s (+160 mL vs. +30 mL; P = 0.009). Radiographic evidence of lung volume reduction 6 months after BLVR was significantly associated with improved survival (adjusted hazard ratio 0.020; 95% confidence interval 0.038–0.650; P = 0.010). Although pneumothorax was more common in the BLVR group (18.9% vs. 3.8%; P = 0.018), death was higher in the no-BLVR group (38.5% vs. 54.5%, P = 0.001), whereas other adverse events were comparable between the groups. Within the subset of 18 patients with PAL, the predominant causes of air-leak included spontaneous secondary pneumothorax (44.0%), parapneumonic effusion/empyema (22.2%), and post-lung resection surgery (16.7%). Following the treatment, the majority (77.8%) successfully had their chest tubes removed. Post-procedural complications were minimal, with two incidences of hemoptysis and one of empyema, all of which were effectively managed.ConclusionsTreatment with EBV provides substantial clinical benefits in the management of emphysema and PAL in the Asian population, suggesting a favorable outcome for this therapeutic approach.

The effectiveness and pharmacoeconomic study of using different corticosteroids in the treatment of hypersensitivity pneumonitis

PurposeInterstitial lung diseases (ILDs) are caused by inflammation and/or fibrosis of alveolar walls resulting in impaired gas exchange. Hypersensitivity pneumonitis (HP) is the third most common type of ILDs. Corticosteroids are the mainstay treatment for HP. The use of intramuscular (IM) betamethasone or intravenous (IV) dexamethasone as weekly pulse doses has shown higher benefit than daily oral prednisolone for HP patients. The aim of this study is to directly compare different corticosteroids in terms of effectiveness and in monetary values and perform an economic evaluation.MethodsOne hundred and seven patients were tested for pulmonary function tests (PFTs) and inflammatory markers to assess the treatment effectiveness. A cost-effectiveness analysis (CEA) was performed. ICERs between 3 treatment groups were calculated.ResultsPost treatment, Krebs von den Lungen-6 (KL-6) levels significantly improved in betamethasone group from 723.22 ± 218.18 U/ml to 554.48 ± 129.69 U/ml (p = 0.001). A significant improvement in erythrocyte sedimentation rate (ESR) occurred in the dexamethasone group from 56.12 ± 27.97 mm to 30.06 ± 16.04 mm (p = 0.048). A significant improvement in forced expiratory volume (FEV1), forced vital capacity (FVC) and six-minute walk distance (6MWD) was observed within the three treatment groups. A significant improvement in oxygen desaturation percentage (SpO2) occurred within dexamethasone and betamethasone groups. Betamethasone and dexamethasone were found more cost-effective than prednisolone as their ICERs fell in quadrant C. Furthermore, ICER between betamethasone and dexamethasone was performed; a small difference in cost was found compared to the higher benefit of betamethasone.ConclusionBetamethasone and dexamethasone were found to be more effective than prednisolone in improving the inflammatory reaction and the clinical features of HP patients. Betamethasone was found to be the best intervention in terms of cost against the effect.

Predictors of Early and Late Lung Function Improvement in Severe Eosinophilic Asthma on Type2-Biologics in the PRISM Study.

The determinants linked to the short- and long-term improvement in lung function in patients with severe eosinophilic asthma (SEA) on biological treatment (BioT) remain elusive. We sought to identify the predictors of early and late lung function improvement in patients with SEA after BioT. 140 adult patients with SEA who received mepolizumab, dupilumab, or reslizumab were followed up for 6months to evaluate improvement in forced expiratory volume in one second (FEV1). Logistic regression was used to determine the association between potential prognostic factors and improved lung function at 1 and 6months of treatment. More than a third of patients with SEA using BioT showed early and sustained improvements in FEV1 after 1month. A significant association was found between low baseline FEV1 and high blood eosinophil count and sustained FEV1 improvement after 1month (0.54 [0.37-0.79] and 1.88 [1.28-2.97] odds ratios and 95% confidence interval, respectively). Meanwhile, among patients who did not experience FEV1 improvement after 1month, 39% exhibited improvement at 6months follow-up. A high ACT score measured at this visit was the most reliable predictor of late response after 6months of treatment (OR and 95% CI 1.75 [1.09-2.98]). Factors predicting the efficacy of biological agents that improve lung function in SEA vary according to the stage of response.

Effects of Chest Mobilization and Breathing Exercises on Respiratory Function, Trunk Stability, and Endurance in Chronic Stroke Patients after Coronavirus Disease.

Background and objectives: This study investigates the effects of chest mobilization and breathing exercises on respiratory function, trunk stability, and endurance in chronic stroke patients who have contracted coronavirus disease (COVID-19). Materials and Methods: Thirty inpatients of a tertiary hospital in South Korea, who had a history of COVID-19 and were diagnosed with stroke within the last 6 months, were randomly assigned to either chest mobilization exercise with breathing exercise (CMEBE) or conservative physical therapy with breathing exercise (CPTBE) groups. The respiratory function, trunk stability, and endurance were measured at baseline and 6 weeks after the interventions. Results: Both CMEBE and CPTBE groups showed improvements in respiratory function, trunk stability, and endurance after the intervention (p < 0.05). However, the CMEBE group showed significantly greater improvements in forced expiratory volume in 1 s (p < 0.05), trunk stability (p < 0.05), and endurance (p < 0.05) than the CPTBE group. No significant intergroup difference was observed in forced vital capacity and peak expiratory flow. Conclusions: The combination of chest mobilization and breathing exercises improved respiratory muscle mobility and endurance, stabilized the trunk, and enhanced balance and the transfer of weight. The findings suggest that this intervention could be beneficial in improving respiratory function and endurance in stroke patients.

Relevance of pleural adhesions for short- and long-term outcomes after lung volume reduction surgery

ObjectivePleural adhesions (PLAs) have been shown to be a possible risk factor for air leak after lung volume reduction surgery (LVRS), but the relevance of PLA for lung function outcome remains unclear. We analyzed our LVRS cohort for the influence of PLA on short-term (ie, prolonged air leak) and long-term outcomes. MethodsRetrospective observational cohort study with 187 consecutive patients who underwent LVRS from January 2016 to December 2019. PLA were defined as relevant if they were distributed extensively at the dorsal pleura; were present in at least at 2 areas, including the dorsal pleura; or present extensively at the mediastinal pleura. In patients with bilateral emphysema, bilateral LVRS was performed preferentially. The objectives were to quantify the association of PLA and rate of prolonged air leak (chest tube >7 days), and the association of PLA with postoperative exacerbations and with forced expiratory volume in 1 second 3 months postoperatively. The associations were quantified with odds ratios for binary outcomes, and with between-group differences for continuous outcomes. To account for missing observations, 100-fold multiple imputation was used. ResultsPLAs were found in 46 of 187 patients (24.6%). There was a 32.6% rate of prolonged air leak (n = 61), mean chest tube time was 7.84 days. A total of 94 (50.3%) LVRSs were unilateral and 93 were bilateral. There was evidence for an association between PLA and the rate of prolonged air leak (odds ratio, 2.83; 95% CI, 1.36 to 5.89; P = .006). There was no evidence for an association between PLA and postoperative exacerbations (odds ratio, 1.11; 95% CI, 0.5 to 2.45; P = .79). There was no evidence for an association between PLA and forced expiratory volume in 1 second (estimate −1.52; 95% CI –5.67 to 2.63; P = .47). Both unilateral and bilateral LVRS showed significant postoperative improvements in forced expiratory volume in 1 second by 27% (8.43 units; 95% CI, 3.66-13.12; P = .0006) and by 28% (7.87 units; 95% CI, 4.68-11.06; P < .0001) and a reduction in residual volume of 15% (−33.9 units; 95% CI, −56.37 to −11.42; P = .003) and 15% (−34.9 units; 95% CI, −52.57 to −17.22; P = .0001), respectively. ConclusionsPatients should be aware of potential prolongation of hospitalization due to PLA. However, there might be no relevant influence of PLA on lung function outcomes.

Mineral water inhalations for bronchial asthma: a meta-analysis.

Bronchial asthma (BA) is a common disease that contributes significantly to the incidence rate and death rate worldwide. A widespread treatment method is the use of inhalations of mineral waters, with conflicting information about their effectiveness. Purpose of the study was to assess the generalized effect power of the course of inhalations of mineral waters on the disease progress in patients with BA. A search of randomized clinical studies in data bases Pubmed, EMBASE, ELibrary, MedPilot amd CyberLeninka, according to PRISMA strategy, published between 1986 and July 2021. Standardized difference of mean values and their 95% of CI were employed for calculation using the random effects model. The meta-analysis drawing on 1266 sources included 14 studies, with 2 of them being randomized controlled clinical studies, including the results of the treatment of 525 patients. All 14 articles contain a conclusion that the inhalation of mineral water has a positive effect on the course of the disease in patients with BA. The analysis demonstrated that the group of patients after mineral water inhalations, compared with the control group, showed improvement of forced expiratory volume (FEV1), expressed both in % of the norm and in liters. The standardized difference of mean values FEV1 (%) (Hedge's g) was 8.2 (95% CI: 5.87 - 10.59; 100%), FEV1 values (liter.) (Hedge's g) was 0.69 (95% CI: -0.33-1.05). A significant heterogeneity of the results of individual studies was found (Q=124.96; tau2 = 14.55, I2 = 69.13%, p<0.0001 and Q=2.35; tau2 = 0, I2 = 0%, p<0.0001). Patients with mild, moderate, and hormone-dependent BA with a controlled and partially controlled disease course, after mineral water inhalations, compared with the control group, demonstrated a statistically significant decrease in the frequency and intensity of the cardinal symptoms of BA and improvement of FEV1.

Characterization of sleep in emerging adults with cystic fibrosis on elexacaftor/tezacaftor/ivacaftor

•Emerging adults (18–25 years of age) have high rates of sleep dysfunction.•CFTR dysfunction has been implicated as a direct cause of sleep disorders.•Elexacaftor/tezacaftor/ivacaftor may improve sleep in emerging adults with CF.•Clinical practice guidelines are needed for sleep disturbances in people with CF. Sleep disturbances are common among youth and adults with cystic fibrosis (CF). Prior to the availability of the most highly effective modulator therapy, elexacaftor/tezacaftor/ivacaftor, 90% of patients with CF identified a need for support to improve sleep quality [[1]Sadicario J.S. Islam L. Bostetter A. Chaudary N. Identifying patient priorities for psychosocial support in an adult cystic fibrosis clinic.Pediatr Pulmonol. 2019; 54: 421PubMed Google Scholar]. In the post elexacaftor/tezacaftor/ivacaftor era, 77% of CF program directors in the United States agreed that sleep disorders are a problem in CF; however, only 10% of programs reported regularly conducting routine, formal sleep screening [[2]Thomas C.S. Brown R.F. Sleep screening for cystic fibrosis patients: a survey of cystic fibrosis programs.Pediatr Pulmonol. 2020; 55: 3358-3363Crossref Scopus (3) Google Scholar]. For adults with CF, studies have reported increased sleep disordered breathing [[3]Shakkottai A. Nasr S.Z. Hassan F. Irani S. O'Brien L.M. Chervin R.D. Sleep-disordered breathing in cystic fibrosis.Sleep Med. 2020; 74: 57-65Crossref Scopus (6) Google Scholar,[4]Reiter J. Gileles-Hillel A. Cohen-Cymberknoh M. et al.Sleep disorders in cystic fibrosis: a systematic review and meta-analysis.Sleep Med Rev. 2020; 51101279Crossref Scopus (21) Google Scholar], a delayed circadian rhythm [[5]Jensen J.L. Jones C.R. Kartsonaki C. Packer K.A. Adler F.R. Liou T.G. Sleep phase delay in cystic fibrosis: a potential new manifestation of cystic fibrosis transmembrane regulator dysfunction.Chest. 2017; 152: 386-393Abstract Full Text Full Text PDF PubMed Scopus (18) Google Scholar], increased symptoms of restless legs syndrome [[6]Jurisch P. Gall H. Richter M.J. et al.Increased frequency of the restless legs syndrome in adults with cystic fibrosis.Respir Med. 2019; 151: 8-10Abstract Full Text Full Text PDF Scopus (4) Google Scholar,[7]Mulette P. Ravoninjatovo B. Guguen C. et al.Insomnia in adults with cystic fibrosis: strong association with anxiety/depression and impaired quality of life.BMC Pulm Med. 2021; 21: 108Crossref Scopus (2) Google Scholar], and insomnia [[7]Mulette P. Ravoninjatovo B. Guguen C. et al.Insomnia in adults with cystic fibrosis: strong association with anxiety/depression and impaired quality of life.BMC Pulm Med. 2021; 21: 108Crossref Scopus (2) Google Scholar]. Sleep has been associated with health-related quality of life (HRQOL) outcomes, including physical, mental, and social health in children [[8]Vandeleur M. Walter L.M. Armstrong D.S. Robinson P. Nixon G.M. Horne R.S.C. Quality of life and mood in children with cystic fibrosis: associations with sleep quality.J Cyst Fibros. 2018; 17: 811-820Abstract Full Text Full Text PDF PubMed Scopus (30) Google Scholar,[9]McMurray J. Widger K. Stephenson A.L. Stremler R. Actigraphic and patient and family reported sleep outcomes in children and youth with cystic fibrosis: a systematic review.J Cyst Fibros. 2022; 21: e49-e82Abstract Full Text Full Text PDF Scopus (0) Google Scholar] and adults [[7]Mulette P. Ravoninjatovo B. Guguen C. et al.Insomnia in adults with cystic fibrosis: strong association with anxiety/depression and impaired quality of life.BMC Pulm Med. 2021; 21: 108Crossref Scopus (2) Google Scholar,[10]Forte G.C. Barni G.C. Perin C. Casarotto F.C. Fagondes S.C. Dalcin Pde T. Relationship between clinical variables and health-related quality of life in young adult subjects with cystic fibrosis.Respir Care. 2015; 60: 1459-1468Crossref PubMed Scopus (12) Google Scholar,[11]Íscar-Urrutia M. Madrid-Carbajal C.J. Rubinos-Cuadrado G. et al.Objective and subjective sleep efficiency in adult patients with cystic fibrosis and impact on quality of life.Lung. 2018; 196: 761-767Crossref Scopus (7) Google Scholar]. Factors associated with sleep disturbances include mucus, reflux, cough, anxiety, depression, and pain [[4]Reiter J. Gileles-Hillel A. Cohen-Cymberknoh M. et al.Sleep disorders in cystic fibrosis: a systematic review and meta-analysis.Sleep Med Rev. 2020; 51101279Crossref Scopus (21) Google Scholar], with self-reported medical marijuana used by >50% of patients with CF for insomnia [[12]Stephen M.J. Chowdhury J. Tejada L.A. Zanni R. Hadjiliadis D. Use of medical marijuana in cystic fibrosis patients.Complement Med Ther. 2020; 20: 323Crossref PubMed Scopus (6) Google Scholar]. CF transmembrane conductance regulator (CFTR) protein is found in the retina and anterior hypothalamus and CFTR dysfunction has been implicated as a cause of sleep dysfunction, with evidence to suggest the CFTR gene may impact regulation of circadian rhythms [[13]Louis M. Staiano P. Micalo L. Chaudary N. Cystic fibrosis and sleep circadian rhythms.Pulm Ther. 2022; 8: 139-147Crossref Scopus (0) Google Scholar]. Use of elexacaftor/tezacaftor/ivacaftor may have a direct impact on sleep beyond the well described benefits of decreased respiratory symptoms including improvements in forced expiratory volume (FEV1) and reductions in pulmonary exacerbations [[14]Graeber S.Y. Vitzthum C. Pallenberg S.T. et al.Effects of elexacaftor/tezacaftor/ivacaftor therapy on CFTR function in patients with cystic fibrosis and one or two F508del alleles.Am J Respir Crit Care Med. 2022; 205: 540-549Crossref PubMed Google Scholar]. One study reported improvements in sleep quality in children and adults taking ivacaftor [[15]McCormick J. Cho D.Y. Lampkin B. et al.Ivacaftor improves rhinologic, psychologic, and sleep-related quality of life in G551D cystic fibrosis patients.Int Forum Allergy Rhinol. 2019; 9: 292-297Crossref PubMed Scopus (34) Google Scholar]. Emerging adulthood (18 to 25 years of age) is a distinct and critical developmental period characterized by identity development, a stage in which young people explore questions of who they are and who they would like to be [[16]Potterton R. Austin A. Robinson L. Webb H. Allen K.L. Schmidt U. Identity development and social-emotional disorders during adolescence and emerging adulthood: a systematic review and meta-analysis.J Youth Adolesc. 2022; 51: 16-29Crossref Scopus (3) Google Scholar]. In addition to identity formation, emerging adults are also exploring and committing to complex choices about education, work, and relationships [[17]Arnett J.J. Emerging adulthood. a theory of development from the late teens through the twenties.Am Psychol. 2000; 55: 469-480Crossref PubMed Scopus (9003) Google Scholar]. Emerging adults with CF must navigate these significant life changes while simultaneously transitioning to independently managing their complex chronic illness [[18]Skedgell K.K. Cao V.T. Gallagher K.A. Anderson B.J. Hilliard M.E. Defining features of diabetes resilience in emerging adults with type 1 diabetes.Pediatr Diabetes. 2021; 22: 345-353Crossref Scopus (6) Google Scholar]. Sleep is also unique among emerging adults, with higher rates of insufficient sleep duration, poor quality sleep, and delayed circadian rhythms [[19]Nicholson L. Bohnert A.M. Crowley S.J. A developmental perspective on sleep consistency: preschool age through emerging adulthood.Behav Sleep Med. 2023; 21: 97-116Crossref Scopus (3) Google Scholar]. We report characterization of patient perspectives on sleep and daytime functioning in emerging adults with CF on elexacaftor/tezacaftor/ivacaftor. This cross-sectional characterization study used an online survey. People with CF (pwCF) ages 18 to 25 years inclusive, English speaking, and currently stable on elexacaftor/tezacaftor/ivacaftor for FDA-approved indications and receiving FDA-approved dosing were recruited from National Jewish Health. Exclusion criteria included pulmonary exacerbation (≥10% decline in percent predicted FEV1 and/or use of systemic antibiotics and/or use of systemic steroids) and/or hospitalization in past month, transplant recipient, diagnosed significant mental health disorder (e.g., schizophrenia, bipolar, PTSD) known to interfere with sleep, and requirement of guardian to support activities of daily living. Participants aged 18 to 25 years inclusive and English speaking without CF (controls) were recruited through peer nomination. Exclusion criteria included a diagnosed chronic illness with daily therapies/medications known to interfere with sleep (e.g., diabetes, hypertension, asthma, GERD), or a diagnosed significant mental health disorder known to interfere with sleep. Sleep. Ten items from validated measures were used to screen for the presence and frequency of symptoms of sleep disordered breathing (snoring, apnea, tired/sleepy during day) [[20]Manzar M.D. Hameed U.A. Alqahtani M. et al.Obstructive sleep apnea screening in young people: psychometric validation of a shortened version of the STOP-BANG questionnaire using categorical data methods.Ann Thorac Med. 2020; 15: 215-222Crossref Scopus (2) Google Scholar], restless legs syndrome [[21]Ferri R. Lanuzza B. Cosentino F.I. et al.A single question for the rapid screening of restless legs syndrome in the neurological clinical practice.Eur J Neurol. 2007; 14: 1016-1021Crossref PubMed Scopus (96) Google Scholar,[22]Fulda S. Allen R.P. Earley C.J. et al.We need to do better: a systematic review and meta-analysis of diagnostic test accuracy of restless legs syndrome screening instruments.Sleep Med Rev. 2021; 58101461Crossref Scopus (10) Google Scholar], and parasomnias (sleep walking/sleep terrors) [[23]Meltzer L.J. Brimeyer C. Russell K. et al.The children's report of sleep patterns: validity and reliability of the sleep hygiene index and sleep disturbance scale in adolescents.Sleep Med. 2014; 15: 1500-1507Crossref PubMed Scopus (31) Google Scholar]. Participants were asked about use of over-the-counter (OTC) sleep aids, melatonin, or marijuana/CBD to facilitate sleep. If endorsed, participants were asked the frequency of use (every night, several nights per week, several nights per month, once a month, less than once a month). PwCF were asked 7 questions about their sleep now, compared to before starting elexacaftor/tezacaftor/ivacaftor. Health-Related Quality of Life (HRQOL). Patient Reported Outcome Measurement Information System (PROMIS®) short forms (4 items each) were used to evaluate HRQOL: Sleep Disturbance, Sleep Related Impairment, Depression, Anxiety, Emotional Support, Informational Support, and Pain Interference [24Buysse D.J. Yu L. Moul D.E. et al.Development and validation of patient-reported outcome measures for sleep disturbance and sleep-related impairments.Sleep. 2010; 33: 781-792Crossref PubMed Scopus (468) Google Scholar, 25Cella D. Riley W. Stone A. et al.The patient-reported outcomes measurement information system (PROMIS) developed and tested its first wave of adult self-reported health outcome item banks: 2005-2008.J Clin Epidemiol. 2010; 63: 1179-1194Abstract Full Text Full Text PDF PubMed Scopus (2800) Google Scholar, 26Pilkonis P.A. Choi S.W. Reise S.P. Stover A.M. Riley W.T. Cella D. Item banks for measuring emotional distress from the patient-reported outcomes measurement information system (PROMIS(R)): depression, anxiety, and anger.Assessment. 2011; 18: 263-283Crossref PubMed Scopus (1165) Google Scholar]. Raw scores were converted to T-scores (mean=50, SD=10) using www.assessmentcenter.net. Demographic Information. Participants self-reported demographic variables. Clinical Data Capture. The electronic medical record was reviewed to collect health information on pwCF, including CF mutations, CF complications, comorbidities, and medications. Descriptive statistics were used to describe participant characteristics and changes in sleep since starting elexacaftor/tezacaftor/ivacaftor. Chi-square analyses were used to compare the percent of pwCF and Control participants on categorical variables. One-way ANOVA was used to compare group differences on continuous HRQOL variables, with Cohen's d effect sizes to examine the magnitude of difference [small=0.2, medium=0.5, large=0.8] [[27]Cohen J. Statistical power analysis for the behavioral sciences.2nd ed. Lawrence Erlbaum Associates, Mahwah, NJ1988Google Scholar]. Pearson correlation was used to examine the association between sleep and HRQOL measures. Continuous variables were normally distributed and free from outliers. Study participants included 34 pwCF and 42 controls. Demographic characteristics are shown in Table 1. Overall, study participants ranged in age from 18 to 25 years (M±SD 23.2 ± 1.9 years), 52.6% were female (n = 40), 85.1% White (n = 63), and 14.5% Hispanic (n = 11). PwCF had a mean BMI of 22.6 ± 3.4 (range 16.0 to 34.1) and a mean FEV1% predicted of 92.3 ± 21.9 (range 36.6 to 128.0). CF characteristics were similar to the general population of pwCF [[28]Cystic Fibrosis Foundation Patient Registry 2021 Annual Data Report Bethesda, Maryland ©2022 Cystic Fibrosis Foundation.Google Scholar] (Table 1).Table 1Characterization of study participants by group [percent (n) unless otherwise stated].CF Group (n = 34)Control Group (n = 42)Test statisticPDemographic CharacteristicsMean Age ± SD22.8 ± 1.923.5 ± 1.9t(74) = −1.640.11GenderX2(2) = 1.290.53 Male44.1 (15)47.6 (20) Female52.9 (18)52.4 (22) Other2.9 (1)–RaceX2(3) = 7.030.07 White97.0 (32)75.3 (31) Black–9.8 (4) Asian–4.9 (2) Multi-racial/Other3.0 (1)9.8 (4)EthnicityX2(1) = 0.370.55 Hispanic88.2 (30)83.3 (35) Non-Hispanic11.8 (4)16.7 (7)Currently WorkingX2(2) = 1.480.48 Full-time52.9 (18)66.7 (28) Part-time20.6 (7)14.3 (6) Not working26.5 (9)19.0 (8)Attending SchoolX2(2) = 5.590.06 Full-time26.5 (9)31.0 (13) Part-time2.9 (1)19.0 (8) Not attending school70.6 (24)50.0 (21)Partner StatusX2(2) = 3.450.18 Single44.1 (15)59.5 (25) Married20.6 (7)7.1 (3) Partnered35.3 (12)33.3 (14)ChildrenX2(1) = 1.560.21 No91.2 (31)97.6 (41) Yes8.8 (3)2.4 (1)Living SituationX2(1) = 0.640.42 Home with parent(s)/guardian(s)29.4 (10)21.4 (9) Independently (including college)70.6 (24)78.6 (33)CF Mutations–– F508del94.1 (32)– G551D8.8 (3)– 1898 + 1G→T5.9 (2)–CF Complications–– Pancreatic insufficiency100.0 (34)– Diabetes44.1 (15)– Impaired glucose tolerance44.1 (15)– Osteopenia38.2 (13)– Non-cirrhosis liver disease29.4 (10)– Arthritis20.6 (7)–Comorbidities–– Chronic sinusitis94.1 (32)– Asthma82.4 (28)– GERD58.8 (20)– Depression44.1 (15)– Anxiety32.4 (11)– Hypertension14.7 (5)–Medications–– Nasal steroids38.2 (13)– Monteleukast32.4 (11)– OTC antihistamine32.4 (11)– SSRI17.6 (6)– Sleep prescription*8.8 (3)–Non-Prescription Sleep AidsOTC Sleep AidX2 = 0.740.39 No73.5 (25)64.3 (27) Yes26.5 (9)35.7 (15)Frequency OTC Sleep AidX2 = 4.560.10 Several nights per week22.2 (2)6.7 (1) At least once a month66.7 (6)40.0 (6) Less than once a month11.1 (1)53.3 (8)Melatonin UseX2 = 0.630.43 No70.6 (24)61.9 (26) Yes29.4 (10)38.1 (16)Frequency Melatonin UseX2 = 2.090.35 Several nights per week10.0 (1)18.8 (3) At least once a month30.0 (3)50.0 (8) Less than once a month60.0 (6)31.3 (5)Marijuana/CBD Use for SleepX2 = 1.810.18 No64.7 (22)78.6 (33) Yes35.3 (12)21.4 (9)Frequency Marijuana/CBD UseX2 = 3.860.15 Several nights per week75.0 (9)44.4 (4) At least once a month16.7 (2)55.6 (5) Less than once a month8.3 (1)0.0 (0)*Trazodone, clonazepam, amitriptyline. Open table in a new tab *Trazodone, clonazepam, amitriptyline. Snoring was more common among controls (pwCF=5.9%, controls=23.8%), X2(1)=4.54, p = 0.03, with no group difference in observed apnea frequency (pwCF=5.9%, controls=2.4%), X2(1)=0.61, p = 0.44. More pwCF reported daytime fatigue/sleepiness (pwCF=50.0%, controls=19.0%), X2(1)=8.16, p = 0.004. Although not significant, more pwCF reported symptoms of restless leg syndrome (pwCF=38.2%, controls=26.2%), X2(1)=1.26, p = 0.26, and parasomnias (sleep walking/sleep terrors) (pwCF=47.1%, controls=33.3%), X2(1)=1.48, p = 0.22. Although not significant, more control participants used OTC sleep aids (pwCF=26.5%, controls=35.7%) and melatonin (pwCF=29.4%, controls=38.1%) to facilitate sleep (Table 1). More pwCF used marijuana/CBD (pwCF=35.5%, controls=21.4%) to facilitate sleep, with 75% of pwCF using marijuana/CBD for sleep several nights per week (vs. 44.4% of controls). Notably, although fewer pwCF used OTC sleep aids, their use was more frequent than controls. Similarly, although fewer pwCF used melatonin, they used significantly higher doses (pwCF=8.3 ± 5.8 mg, controls=3.8 ± 2.9 mg), t(24)=2.69, p = 0.01. Eighty-eight to 97% of pwCF reported either no change or improvements in sleep since starting elexacaftor/tezacaftor/ivacaftor (Fig. 1). The most notable change was a decrease in the frequency of medications to facilitate sleep, with almost a third of pwCF reporting improvements. Open ended responses also noted “feeling less mucus in my lungs,” “needing less sleep,” and “wake up from coughing better.” Since starting elexacaftor/tezacaftor/ivacaftor, 29% (n = 10) of pwCF reported no change in sleep, 35% (n = 12) reported ≥1 area of improvement, and no worsening symptoms, 18% (n = 6) reported ≥1 area of improvement and 1 worsening symptom, and 18% (n = 6) reported ≥1 area of sleep getting worse, and no improvements. As seen in Table 2, compared to controls, pwCF reported significantly greater sleep disturbances (d = 0.46) and more pain (d = 0.66). Although not statistically significant, small to medium effect sizes highlighted more sleep-related daytime impairment (d = 0.35) and less social support in terms of the availability of helpful information or advice (d = -0.37) in pwCF compared to controls.Table 2PROMIS health-related quality of life (HRQOL) mean (SD) T-scores by group.CF Group (n = 34)Control Group (n = 42)FPCohen's dSleep Disturbance51.2 (6.0)48.2 (7.0)3.910.050.46Sleep-Related Impairment55.2 (7.4)52.5 (8.1)2.240.140.35Anxiety56.5 (9.5)54.9 (8.7)0.600.440.18Depressive Symptoms51.8 (9.7)51.1 (9.1)0.100.760.07Emotional Support55.6 (9.1)55.7 (8.2)0.010.94−0.01Informational Support56.0 (10.5)59.3 (7.1)2.760.10−0.37Pain49.8 (8.7)44.9 (5.9)8.730.0040.66 Open table in a new tab For pwCF, greater sleep disturbances were associated with increased anxiety (r = 0.58, p<0.001) and depressive symptoms (r = 0.50, p = 0.002), lower emotional support (r = -0.35, p = 0.04) and information support (r = -0.39, p = 0.02), and more pain (r = 0.32, p = 0.06). Greater sleep-related impairment was associated with increased anxiety (r = 0.59, p<0.001) and depressive symptoms (r = 0.49, p = 0.003), and lower information support (r = -0.36, p = 0.04). For control participants, greater sleep disturbances were associated with increased anxiety (r = 0.46, p = 0.02) and depressive symptoms (r = 0.44, p = 0.003). Greater sleep-related impairment was associated with increased anxiety (r = 0.46, p = 0.02) and depressive symptoms (r = 0.64, p<0.001). This study highlights that elexacaftor/tezacaftor/ivacaftor may improve sleep in some emerging adults with CF. Despite this improvement, sleep remains a significant concern, with pwCF more frequently using sleep aids, reporting poorer quality sleep, and more impacts on quality of life than age-matched controls. Due to the small sample size, many of the group comparisons were not significantly different, however, the results were clinically meaningful and may be statistically significant if repeated in a larger sample. Study limitations also include the correlational study design, self-selection bias, recall bias potentially influenced by time on elexacaftor/tezacaftor/ivacaftor (i.e., questions only asked after participants were already on treatment), and overall transformative health improvements frequently experienced by people taking this therapy, as well as the lack of data on control participant BMI that may be related to sleep disordered breathing. As a preliminary characterization of this sample, further research is needed that will objectively characterize sleep with actigraphy and polysomnography, and further explore the relationship between sleep disturbances and HRQOL among pwCF. Future studies should also include information about symptoms of daytime sleepiness, alcohol use, exercise, caffeine consumption, and screen time. Further investigation of the impact of elexacaftor/tezacaftor/ivacaftor on sleep is warranted, including a comparison with pwCF who are not eligible for CFTR modulator therapy. Together this knowledge can facilitate development of clinical practice guidelines for the screening and treatment of sleep disturbances in pwCF.

ICU Physical Therapy Benefits for Patients Infected with SARS-CoV-2

"Background: SARS-CoV-2 is a still new condition whose etiologies and physiopathogensis are still incompletely elucidated, one of the certain things about this condition being the fact that it causes a multisystemic pathological affect. Material and methods: The study was conducted on a sample of 10 patients aged between 40 and 65 years from the Intensive Care Unit. The main inclusion criterion was the presence of chronic respiratory failure exacerbated by SARS-CoV-2 pneumonia, with all patients following the same recovery protocol. Results: The results showed improvement in forced expiratory volume, forced vital capacity, overall mobility, and in quality of life. Conclusion: Respiratory physiotherapy determines a significant improvement of the respiratory function in the patients infected with SARS-CoV-2"

Multistrain Probiotics Supplement Alleviates Asthma Symptoms via Increasing Treg Cells Population: A Randomized, Double-Blind, Placebo-Controlled Trial

Introduction: The favorable effects of probiotics have been demonstrated in allergic disorders. However, the underlying immunological mechanisms are poorly understood. In the present study, we investigated the improvement of clinical symptoms and immunological balance after receiving probiotics in patients with asthma. Methods: The present study was a randomized, double-blind, placebo-controlled trial in which 40 patients with asthma were enrolled. They were treated with probiotics or placebo: 1 capsule/day for 8 weeks. Pulmonary function test, percentage of CD4⁺ CD25⁺ FoxP3⁺ Tregs, and gene expression of T-bet, GATA-3, RORγt, and Foxp3 in PBMCs were assessed at baseline and after treatment. Results: Our results showed a significant increase in the expression of FoxP3 and CD4⁺ CD25⁺ FoxP3⁺ Tregs population, while RORγt and GATA3 expression were reduced. In addition, pulmonary function tests showed a significant improvement in forced expiratory volume and forced vital capacity after receiving probiotics. Discussion/Conclusion: Our findings demonstrate that 8-week treatment with probiotic supplementation can control T-helper 2-predominant and Th17 pro-inflammatory responses and improve forced vital and forced expiratory volume in asthmatic patients. It seems probiotics can be used besides common treatments for patients with asthma.

Long-term efficacy of dupilumab in asthma with or without chronic rhinosinusitis and nasal polyps

BackgroundCoexisting chronic rhinosinusitis and nasal polyps (CRS-NPs) substantially increases the disease burden of asthma. Dupilumab, a fully human monoclonal antibody, has established efficacy and an acceptable safety profile in asthma and CRS with NP. ObjectiveTo evaluate long-term dupilumab efficacy in TRAVERSE (NCT02134028) patients with uncontrolled, moderate-to-severe (QUEST) or oral corticosteroid (OCS)-dependent (VENTURE) asthma with or without coexisting CRS-NP. MethodsIn TRAVERSE, 317 of 1530 (21%) QUEST and 61 of 187 (48%) VENTURE patients had self-reported CRS-NP; they received subcutaneous 300 mg dupilumab every 2 weeks up to 96 weeks. Patients were categorized by parent study treatment group (placebo/dupilumab, dupilumab/dupilumab). End points included annualized asthma exacerbation rates and mean change from parent study baseline in prebronchodilator forced expiratory volume in 1 second, Asthma Control Questionnaire 5 score, Asthma Quality of Life Questionnaire score, and OCS dose. ResultsPatients with coexisting CRS-NP had higher OCS dose and a history of more exacerbations. Concluding TRAVERSE, exacerbation rates decreased from 2.39 to 0.32 and 2.32 to 0.35 in dupilumab/dupilumab and 2.36 to 0.41 and 2.36 to 0.45 in placebo/dupilumab by week 96 from QUEST and VENTURE baselines, respectively. Non-CRS-NP results were similar. Improvements in forced expiratory volume in 1 second, Asthma Control Questionnaire 5 score, and Asthma Quality of Life Questionnaire score during parent studies were maintained in TRAVERSE; placebo/dupilumab patients achieved similar improvements to dupilumab/dupilumab by week 48. By week 96, 71% and 39% of OCS-dependent patients with CRS-NP and 83% and 47% without CRS-NP treated with dupilumab/dupilumab and placebo/dupilumab, respectively, stopped OCS. ConclusionLong-term dupilumab efficacy was maintained in patients with asthma with or without self-reported coexisting CRS-NP, including OCS-sparing effects observed in OCS-dependent severe asthma. Clinical Trial RegistrationClinicalTrials.gov Identifiers: NCT02528214, NCT02414854, and NCT02134028.

Sensitivity of FEV1 and Clinical Parameters in Children With a Suspected Asthma Diagnosis

Asthma is the most common chronic disease in children and a robust diagnosis is crucial to optimize patient care and reduce its burden. To diagnose asthma in children, the Global Initiative for Asthma (GINA) recommendations propose a 12% improvement in forced expiratory volume in 1 second (FEV1) after a bronchodilation test. Nevertheless, such a criterion is rarely confirmed in these patients in clinical practice. The objective of this study was to evaluate the sensitivity of spirometric and clinical parameters in identifying children with possible asthma. The VERI-VEMS Study is a multicenter international retrospective cohort study. Data were collected, from January 2008 until January 2019, for all consecutive children (aged 5-18 years), with a diagnosis of asthma, who performed a spirometry at the time of the diagnosis. We compared the sensitivity of the reversibility criterion proposed by GINA guidelines, with other spirometric and clinical variables, using physician-diagnosed asthma and response to treatment as the standard. The study included 871 children. The reversibility criterion of 12% of FEV1 showed a sensitivity of 30.4%. The 3 best spirometric or clinical criteria were the presence of dry cough, or wheezing or atopy and dry cough, or wheezing or exercise-induced dyspnea, with a sensitivity reaching 99.5%, with no added value of the spirometric parameters in the calculation of the cumulated sensitivity for the diagnosis of pediatric asthma. Postbronchodilator reversibility of 12%, although essential for patients' follow-up, has an insufficient low sensitivity in reaching a diagnosis of asthma in pediatric patients, compared with a combination of clinical symptoms, that show a better sensitivity. Further studies on specificity will help clarify the role of this change in the diagnostic paradigm in formally diagnosing children with asthma.

Modulator Therapy in Cystic Fibrosis Patients with cis Variants in F508del Complex Allele: A Short-Term Observational Case Series.

Previous studies reported the influence of cis variants in F508del cystic fibrosis (CF) patients in their responses to CFTR modulators. The current study is a prospective, observational study involving three patients with CF and pancreatic insufficiency, carrying a complex allele including F508del with A238V, I1027T, or L467F. We report clinical data before and after 4 weeks of treatment with tezacaftor (TEZ)/ivacaftor (IVA), elexacaftor (ELX)/TEZ/IVA, and lumacaftor (LUM)/IVA for patients with complex alleles A238V, I1027T, and L467F, respectively. The 50-year-old patient bearing F508del;A238V/D1152H showed a normal sweat test (13 mEq/L) and improvements in forced expiratory volume in the first second (FEV1) (+7 points), body mass index (BMI) (+0.85), and respiratory CF Questionnaire-Revised (CFQ-R) domain (+22.2 points). The 12-year-old patient bearing F508del;I1027T/R709X showed an improvement in a sweat test (−40 mEq/l), FEV1 (+9 points) and the respiratory CFQ-R domain (+16.7 points). No changes in outcomes were observed for the 6-year-old patient F508del;L467F/F508del. Our data highlight that the reported variants do not modify the phenotypic expression of F508del. Searching L467F is crucial in CF patients with F508del nonresponsive to ELX/TEZ/IVA. Further data are needed to evaluate the clinical effect of these variants after a longer follow up.

The Role of Dual Bronchodilation and the Conscientious Use of Inhaled Corticosteroid in COPD

Chronic obstructive pulmonary disease (COPD) is a global public health burden that stands out as a leading cause of mortality around the world, especially in less developed countries. COPD treatment should be centered on the individual necessities of each patient, integrating pharmacological therapy, immunization, nutritional support, pulmonary rehabilitation and control of comorbidities. Combining a long-acting antimuscarinic (LAMA) with a long-acting beta2-agonist (LABA) bronchodilator has proven to be more effective than monotherapy with LABA or LAMA, in terms of the functional improvement of forced expiratory volume (FEV1), symptoms and life quality and may be helpful in patients with progressive dyspnea. The eosinophil blood count is a simple biomarker that could guide personalized treatment strategies by identifying patients with greater clinical benefits of inhaled corticosteroid (ICS) treatment. However, one critical concern is the increased risk of pneumonia in individuals treated with ICS.

Complete response to anti-interleukin-5 biologics in a real-life setting: results from the nationwide Danish Severe Asthma Register.

BackgroundPhase III regulatory trials show that anti-interleukin (IL)-5 biologics efficiently reduce exacerbations and the use of maintenance oral corticosteroids (mOCS) in patients with severe eosinophilic asthma. However, patients eligible for these trials differ significantly compared with real-life severe asthma populations. Therefore, our aim was to explore efficacy in a real-life setting. The Danish Severe Asthma Register (DSAR) is a complete, nationwide register that comprises all Danish patients on biological therapy for severe asthma.MethodsThis prospective study identified patients in the DSAR who were complete responders to anti-IL-5 biologics after 1 year of treatment. A complete response was defined as resolution of the parameter setting the indication, i.e. recurrent exacerbations and/or use of mOCS.ResultsA total of 289 out of 502 (58%) patients were complete responders to anti-IL-5 biologics after 12 months. Complete responders had greater improvements in forced expiratory volume in 1 s and Asthma Control Questionnaire (ACQ) score compared with noncomplete responders (Δ 210 versus 30 mL; p<0.0001 and Δ −1.04 versus −0.68; p=0.016, respectively). A complete response was predicted by age at onset, less severe disease at baseline (i.e. no mOCS and lower ACQ score) and higher blood eosinophils.ConclusionsMore than half of Danish patients treated with anti-IL-5 biologics for severe asthma achieve a complete response to treatment, thereby becoming free from asthma exacerbations and the need for mOCS. Complete responders also achieved superior effects on lung function and symptoms compared with noncomplete responders.

Impact of pharmacotherapy with tiotropium/olodaterol on the pulmonary function in COPD patients depending on the Arg16Gly polymorphism of ADRB2 gene

BACKGROUND. Chronic obstructive pulmonary disease (COPD) is a widespread chronic disease, that can be prevented and treated. Internal or genetic factors play a significant role in the COPD development.&#x0D; OBJECTIVE. To investigate a response to the tiotropium/olodaterol treatment in patients with different ADRB2 gene polymorphism.&#x0D; MATERIALS AND METHODS. 100 patients with the diagnosis of COPD were included into the study. Pulmonary function testing was performed during all study visits. All patients received treatment according to GOLD 2019, which included a combination of long-acting b2-agonists and long-acting muscarinic antagonists. According to the results of genetic testing all patients were divided into three groups: Arg16Arg – 23 patients (23 %), Arg16Gly – 39 (39 %), Gly16Gly – 38 (38 %).&#x0D; RESULTS. Groups did not differ by sex, age, part of smokers, COPD duration. There was a significant difference in force vital capacity (FVC), which was 66.92±4.33 % in Arg16Arg group, 79.75±3.51 % in Arg16Gly group and 76.59±2.73 % in Gly16Gly group (p=0.05). There was a weak negative correlation between Arg16Arg genotype and FVC (r=-0.204; p=0.043). In regression analysis Arg16Arg genotype was associated with 10.52 % lower FVC on average (odds ratio -10.523; 95 % confidence interval from -20.502 to -0.544; p=0.039). A statistically significant improvement of forced expiratory volume in the first second (FEV1) and FVC was observed in all groups during the study (p&lt;0.001).&#x0D; CONCLUSIONS. Arg16Arg genotype was associated with the lowest FVC values during all study visits. Combination of tiotropium/olodaterol was effective in improving pulmonary function in patients with different ADRB2 genotypes, which was demonstrated by a significant improvement of FEV1 and FVC in study groups during the study.

Acute Effect of Bronchodilator on Intrathoracic Airway Wall Compliance in COPD Patients

PurposeIn patients with chronic obstructive pulmonary disease (COPD), bronchial responsiveness after acute administration of short acting bronchodilators is conventionally assessed by measuring the improvement of forced expiratory volume in the first second (FEV1) during a maximal forced expiratory maneuver. This study aimed to measure the variation of intrathoracic airway wall compliance (AWC) after acute administration of short acting beta-2 agonist in COPD patients since this might influence the final modification of airway caliber during maximal expiratory effort and the resulting bronchodilation as inferred by FEV1 changes.MethodsIn a group of 10 patients suffering from COPD, intrathoracic AWC was measured at middle (50% of Forced Vital Capacity (FVC) and low (75% of FVC) lung volumes using the interrupter method during forced expiratory maneuver in basal conditions and after acute inhalation of albuterol (salbutamol) (400 mcg by MDI). Ten healthy subjects were examined similarly as a control group.ResultsLower values of baseline intrathoracic AWC at both lung volumes were found in COPD patients (1.72 ± 0.20 ml/cmH2O and 1.08 ± 0.20 ml/cmH2O, respectively) as compared to controls (2.28 ± 0.27 ml/cmH2O and 1.44 ± 0.22 ml/cmH2O, respectively) (p < 0.001). In COPD patients, AWC increased significantly at both lung volumes after salbutamol, amounting to 1.81 ± 0.38 ml/cmH2O and 1.31 ± 0.39 ml/cmH2O, respectively (p < 0.01), but the relative change was not different from that observed in controls.ConclusionIn COPD patients, AWC is reduced compared to controls, but after bronchodilator, the intrathoracic airways become more compliant. The consequent increased collapsibility under high positive pleural pressure could limit the airway caliber improvement seen after bronchodilator, as assessed by the FEV1 changes during the forced expiratory maneuver, underestimating the effective bronchodilation achieved in these patients.

Meta-analysis and Systematic Review of Bronchoscopic Lung Volume Reduction Through Endobronchial Valves in Severe Emphysema.

Pharmacologic therapeutics for advanced emphysema have limited benefit. Bronchoscopic lung volume reduction with endobronchial valves (EBVs) have reported improvements in lung function, breathlessness, and quality of life through randomized clinical trials, with less morbidity as comparted to Surgical Lung volume Reduction. We here present a Meta-analysis and systematic review of bronchoscopic lung volume reduction in advanced chronic obstructive lung disease patients. PubMed (NLM), Embase (Elsevier), and Web of Science (Clarivate Analytics) search was conducted using a combination of keywords and subject headings. The search was confined to the last 15 years and was completed on October 23, 2020. Only placebo-controlled randomized control trials of emphysema patients with EBV were included. Quality assessment was done by 2 independent reviewers. Nine studies were included for the meta-analysis with a total number of 1383 patients of whom 888 received EBV and 495 standard of care (SOC) medications. Our Metanalysis show statistically significant improvement in forced expiratory volume in first second, percentage forced expiratory volume in first second, St. George's respiratory questionnaire, and 6-minute walk distance in EBV group compared with SOC. Residual volume had statistically significant reduction after EBV placement compared with SOC. These differences continued to be present during short-term (<=6 mo) and long-term follow-up (>=6 mo). These improvements were even higher when the EBV patients'. Collateral ventilation was negative/fissure was intact (CV-/FI >90%). The rate of hemoptysis and pneumothorax was higher in the EBV group compared with SOC, however, did not lead to increased fatal outcomes. In conclusion, EBV has favorable effects on patients' outcomes in patients who have heterogeneous emphysema particularly with no collateral ventilation.

How the cost-effectiveness results change in the China health policy environment: an economic evaluation of glycopyrrolate/formoterol for the treatment of COPD

Objective To investigate the cost-effectiveness of glycopyrrolate/formoterol compared with tiotropium bromide for the treatment of moderate-to-severe COPD in China and discuss the influence of healthcare policies on the economic evaluation. Methods A Markov model with seven disease states was built to evaluate the lifetime cost-effectiveness of glycopyrrolate/formoterol from the perspective of the Chinese healthcare sector. Drug prices both before and after the negotiation were applied to discuss the influence on the economic evaluation results. Exacerbation and adverse event were included in each cycle. The improvement of forced expiratory volume in 1 second (FEV1) and incidence rate of exacerbation were derived from pooled PINNACLE analysis. Mortality rates from Chinese life tables were adjusted using hazard ratios. Direct medical costs were modeled in accordance with the perspective chosen. Health resource utilization were derived from previous studies and expert’s opinions. Life-years gained, quality-adjusted life years (QALYs), and incidence of exacerbation were simulated as the health outcomes. One-way sensitivity analysis and probability analysis were conducted to explore the robustness of the base case results. Several scenario analyses were also designed. Results Glycopyrrolate/formoterol generated an additional 0.0063 LYs and 0.0032 QALYs with lower lifetime costs compared with tiotropium (CNY 27,854 vs. CNY 33,189) and was proved to be the dominant strategy in the base case analysis. The one-way sensitivity analysis confirmed the robustness of the base case results. The probabilities of glycopyrrolate/formoterol being cost-effective were 96.5, 95.7, and 93.0% when CNY 72,000 (1 time GDP per capital), CNY 108,000, and CNY 216,000 were used as thresholds, respectively. Compared with the scenario where price before negotiation was used, the cost-effectiveness based on current price was significantly increased. Conclusion Glycopyrrolate/formoterol was demonstrated to be a clinically and cost-effective treatment for moderate-to-severe COPD in China using the latest price. The negotiation policy could increase the cost-effectiveness and benefit the patients.

Targeting Downstream Type 2 Cytokines or Upstream Epithelial Alarmins for Severe Asthma

Biologics, including omalizumab, mepolizumab, benralizumab, and dupilumab, targeting downstream IgE, cytokines IL-5, and IL-4/13, respectively, have shown promising effects in terms of reduction in annualized asthma exacerbation rates (AER), oral corticosteroid-sparing effects, improvements in forced expiratory volume in 1 second, and improved Asthma Control Questionnaire scores. However, despite these welcome advances, approximately 30% of patients with severe asthma receiving biologics tailored to their specific downstream type 2 biomarkers, including total IgE, peripheral blood eosinophils, and fractional exhaled nitric oxide, do not experience meaningful improvements in their AER. Instead of blocking downstream cytokines, targeting upstream epithelial alarmins, including IL-33, thymic stromal lymphopoietin, and IL-25, has been proposed to tackle the immunologic heterogeneity of asthma. This review article aims to pragmatically summarize the latest key clinical data on antialarmin therapies in severe asthma and put these findings into context with regard to currently available downstream cytokine blockers.

Effect of montelukast therapy on clinical course, pulmonary function, and mortality in patients with COVID-19.

The inflammatory/anti‐inflammatory balance has an important role in the clinical course of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) (coronavirus disease [COVID‐19]) infection, which has affected over 200 million people since it first appeared in China in December 2019. This study aimed to determine the effectiveness of montelukast, which has known anti‐inflammatory and bronchodilatory effects, in these patients. The prospective randomized controlled study included 180 patients who were hospitalized in the infectious diseases department of our hospital between May and July 2021 and were diagnosed with the delta variant of SARS‐CoV‐2 by real‐time polymerase chain reaction of nasopharyngeal swabs. The patients were divided into three groups and received only standard treatment according to national guidelines (Group 1) or standard treatment plus 10 mg/day montelukast (Group 2) or 20 mg/day montelukast (Group 3). Laboratory parameters and pulmonary function tests (PFTs) at admission and on Day 5 of treatment were compared. Comparison of laboratory parameters on Day 5 showed that Groups 2 and 3 had significantly lower levels of lactate dehydrogenase, fibrinogen, D‐dimer, C‐reactive protein, and procalcitonin compared with Group 1 (p = 0.04, 0.002, 0.05, 0.03, and 0.04, respectively). In the comparison between Groups 2 and 3, only fibrinogen was significantly lower in Group 3 (p = 0.02). PFT results did not differ between the groups at admission, while on Day 5, only Group 3 showed significant improvements in forced expiratory volume in 1 s, forced vital capacity, and peak expiratory flow 25–75 compared with admission (p = 0.001 for all). Montelukast may be beneficial in COVID‐19 patients to maintain the inflammatory/anti‐inflammatory balance, prevent respiratory failure through its bronchodilator activity, and reduce mortality.