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Background and objective A proportion of patients with fibrotic hypersensitivity pneumonitis (fHP) follow a progressive disease course despite immunosuppressive treatment. Little is known about predictors of mortality in fHP. We aimed to investigate the impact of short-term lung function changes in fHP on mortality. Methods Baseline demographics for 145 consecutive patients with a multi-disciplinary team diagnosis of fHP, as well as baseline and 1-year follow-up of lung function, baseline echocardiographic findings, bronchoalveolar lavage (BAL) cellularity and all-cause mortality were recorded. Changes in forced vital capacity (FVC) ≥ 5% and ≥10%, and diffusion capacity of the lung for carbon monoxide (DLCO) ≥ 10% and ≥15% at 1 year were calculated. Cox proportional hazards analysis was performed to test for associations with mortality. Results Baseline lung function severity, age, presence of honeycombing on computed tomography (CT) and echocardiographic pulmonary arterial systolic pressure (PASP) ≥ 40 mm Hg were associated with early mortality, while BAL lymphocytosis was associated with improved survival. A decline in FVC ≥ 5% (hazard ratio [HR]: 3.10, 95% CI: 2.00–4.81, p

Background To quantify the potential decline in dynamic lung volumes following coronavirus disease 2019 (COVID-19) in the general population. Methods A prospective matched cohort study of adult Copenhagen General Population Study (CGPS) participants with a prepandemic spirometry available. CGPS individuals with positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) polymerase chain reaction (PCR) test performed repeat spirometry, a questionnaire regarding respiratory symptoms, and diffusing capacity test for carbon monoxide. A matched uninfected CGPS control sample was used, and simple regression and linear mixed effect models were computed to study lung function decline. Results A total of 606 individuals were included; 92/107 (85.9%) with positive SARS-CoV-2 PCR test experienced coronavirus disease 2019 (COVID-19) symptoms and 12 (11.2%) were hospitalized. Spirometry was performed at median 5.6 months (interquartile range, 3.9–12.8) after positive SARS-CoV-2 PCR test. COVID-19 was associated with adjusted 7.3 mL (95% confidence interval [CI], .3–14.3) and 22.6 mL (95% CI, 13.1–32.0) steeper decline in annual forced expiratory volume in first second (FEV1) and FVC or total 113.8 and 301.3 mL lower FEV1 and FVC from baseline to follow-up. Results were robust in analyses restricted to individuals not requiring hospitalization. Conclusions COVID-19–related declines of dynamic lung volume in the general population not requiring hospitalization were small but measurable.

Objective The Outcome Measures in Rheumatology (OMERACT) is a research organization focused on improving health care outcomes for patients with autoimmune and musculoskeletal diseases. The Connective Tissue Disease-Interstitial Lung Disease (CTD-ILD) Working Group on Lung Physiology is a group within OMERACT charged with identifying outcome measures that should be implemented in studies of patients with CTD-ILD. The OMERACT Filter 2.1 is an evidence-based algorithm used to identify outcome measures that are truthful, feasible, and able to discriminate between groups of interest. Our objective was to summate evidence (published literature, key opinion leader input, patient perspectives) that would influence the CTD-ILD Working Group's vote to accept or reject the use of two measures of lung physiology, the forced vital capacity (FVC) and the diffusion capacity of carbon monoxide (DLco) for use in randomized controlled trials (RTCs) and longitudinal observational studies (LOSs) involving patients with systemic sclerosis associated ILD (SSc-ILD). Methods Patient Research Partners (those afflicted with SSc-ILD) and the CTD-ILD Working Group on Lung Physiology were polled to assess their opinion on the FVC and DLco in terms of feasibility; the CTD-ILD Working Group was also queried on these instruments’ face and content validity. We then conducted a systematic literature review to identify articles in the SSc-ILD population that assessed the following measurement properties of FVC and DLco: (1) construct validity, (2) test-retest reliability, (3) longitudinal construct validity, (4) clinical trial discrimination/sensitivity to detect change in clinical trials, and (5) thresholds of meaning. Results were summarized in a Summary of Measurement Properties (SOMP) table for each instrument. OMERACT CTD-ILD Working Group members discussed and voted on the strength of evidence supporting these two instruments and voted to endorse, provisionally endorse, or not endorse either instrument. Results Forty Patient Research Partners reported these two measures are feasible (are not an unnecessary burden or represent an infeasible longitudinal assessment of their disease). A majority of the 18 CTD-ILD Working Group members voted that both the FVC and DLco are feasible and have face and content validity. The systematic literature review returned 1,447 non-duplicated articles, of which 177 met eligibility for full text review. Forty-eight studies (13 RCTs, 35 LOSs) were included in the qualitative analysis. The FVC SOMP table revealed high quality, consistent data with evidence of good performance for all five measurement properties, suggesting requisite published evidence to proceed with endorsement. The DLco SOMP table showed a lack of data to support test-retest reliability and inadequate evidence to support clinical trial discrimination. There was unanimous agreement (15 [100%]) among voting CTD-ILD Working Group members to endorse the FVC as an instrument for lung physiology in RCTs and LOSs in SSc-ILD. Based on currently available evidence, DLco did not meet the OMERACT criteria and is not recommended for use in RCTs to represent lung physiology of SSc-ILD. The OMERACT Technical Advisory Group agreed with these decisions. Conclusion The OMERACT Filter 2.1 was successfully applied to the domain of lung physiology in patients with SSc-ILD. The FVC was endorsed for use in RCTs and LOSs based on the Working Group's vote; DLco was not endorsed.

Yao-Kuang Wu,1,2 Wen-Lin Su,1,2 Mei-Chen Yang,1,2 Sin-Yi Chen,1 Chih-Wei Wu,1 Chou-Chin Lan1,2 1Division of Pulmonary Medicine, Department of Internal Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City, Taiwan; 2School of Medicine, Tzu-Chi University, Hualien, TaiwanCorrespondence: Chou-Chin LanDivision of Pulmonary Medicine, Department of Internal Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, No. 289, Jianguo Road, Xindian District, New Taipei City, TaiwanTel +886-2-66289779 ext 5709Fax +886-2-66289009Email bluescopy@yahoo.com.twBackground: Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory disease with exacerbations causing hospitalizations, morbidity, and mortality. COPD exacerbation causes a substantial health impact, and its subtypes might differ in prognosis and treatment response.Methods: This study evaluated the factors of COPD exacerbations and explored the probabilities of frequent severe COPD exacerbations. Categorical and continuous variables between groups were compared. The hazard ratio (HR) and the probability of no hospital readmission were also estimated.Results: A total of 617 COPD patients were enrolled and comprised the frequent exacerbator (N = 226) and the non-frequent exacerbator (N = 391) groups. The frequent exacerbator group significantly displayed a higher eosinophil count (EC; p=0.004), a higher percentage of the frequent severe acute exacerbation history before the index hospitalization (IH; p < 0.001), a lower FEV1 value (p=0.001), and a higher triple combination inhaler prior and following the IH (p < 0.001 and p=0.002) than the non-frequent exacerbator one. Increasing age (aOR of 1.02), higher EC (aOR of 1.09), and lower FEV1 value (aOR of 0.72) were significantly associated with an increased hospital readmission risk. The readmission rate and risk were higher in patients with a history of frequent severe acute exacerbation (aHR of 3.38) than those without severe acute exacerbation. Cases treated with the triple combination inhaler before the IH had a higher readmission rate and risk than non-users.Conclusion: Patients with EC ≥ 2%, FEV1 < 50%, or frequent severe acute exacerbation history before the IH have a higher risk of being diagnosed with a frequent exacerbator phenotype. Besides, higher age, triple combination inhaler before the IH, and smoking might be independently correlated with the frequent readmission risk within 1-year post-exacerbation. A better comprehension of the COPD exacerbation mechanism may further identify the best course of preventative strategy and lead to novel interventions.Keywords: chronic obstructive pulmonary disease, COPD, forced expiratory volume in one second, FEV1, forced vital capacity, FVC, index hospitalization, eosinophil count

Introduction: Diabetes mellitus is a leading public health problem all over the world. Diabetesmellitus is a risk factor that precipitating microvascular as well as macro-vascular pathologies.Several respiratory alterations have been reported in associations with Diabetes Mellitus. Therefore,the present study was designed to determine the effect of the disease on respiratory function inpatients with diabetes. Method & material: For this study 54 Diabetes Mellitus patients wereselected using simple random sampling from the diabetic clinic. 54 Non-diabetic, age & sex-matchedsubjects were also taken from teaching and non-teaching employees of the hospital for comparison.Result: In our study there was a statistically significant decrease in the level of FVC in DM patientscompared to healthy male subjects. There was a statistically significant increase in the level of ratioof FEV1/FVC. A more sensitive index of early disease is FEV1/ FVC ratio. Conclusion: Spirometricvalues were consistently lower in subjects with diabetes mellitus than in non-diabetics. Subjects withpoorer diabetic control have a worse spirometric function. We conclude that strict glycaemic control& regular breathing exercises to strengthen the respiratory muscles may improve the pulmonaryfunction test in patients.

Background: Motor Neuron Disease (MND) is a progressive neurodegenerative disorder leading to respiratory muscle weakness with dyspnoea, morning headaches, orthopnoea, poor concentration, unrefreshing sleep, fatigue and daytime somnolence. Respiratory failure is the primary cause of death in those with MND. Methods: Although guidelines suggest the use of non-invasive ventilation (NIV) in MND, there lacks clear guidance as to when is the optimal time to initiate NIV and which markers of respiratory muscle decline are the best predictors of prognosis. There have been a number of studies that have found a significant survival advantage to the use of NIV in MND. Similarly, in quality-of-life questionnaires, those treated with NIV tend to perform better and maintain a better quality of life for longer. Furthermore, studies also suggest that improved compliance and greater tolerance of NIV confer a survival advantage. Results and Discussion: Forced Vital Capacity (FVC) has traditionally been the main pulmonary function test to determine the respiratory function in those with MND; however, FVC may not be entirely reflective of early respiratory muscle dysfunction. Evidence suggests that sniff nasal inspiratory pressure and maximum mouth inspiratory pressure may be better indicators of early respiratory muscle decline. These measures have been shown to be easier to perform later in the disease, in patients with bulbar onset disease, and may indeed be better prognostic indicators. Conclusion: Despite ongoing research, there remains a paucity of randomised controlled data in this area. This review aims to summarise the evidence to date on these topics.

Background The course of hypersensitivity pneumonitis (HP) is characterized by variable patterns of disease progression. Refractory HP is defined as poor or lack of response to different modalities of treatment with worsening of the functional status. Aim To assess the causes of refractory HP and to evaluate the correlation between disease progression and different histopathologic findings in patients with HP. Patients and methods We included 20 patients who were diagnosed primarily as HP and proved to be refractory to treatment. All patients were subjected to the following: complete history taking and clinical examination, spirometry, 6-min walk test, high-resolution CT chest, echocardiography, and transbronchial lung biopsy. Results Female sex was predominant among the studied patients. The mean age of our patients was 39.9±13.49 years. Overall, 65% of these patients were raising birds, but the offending agent was not identified in 30% of patients. Almost all patients presented with restrictive lung functions (mean forced vital capacity=59±10%), and radiologically, they mainly presented with centrilobular ground-glass and nodular opacities. Histopathological results showed that there was isolated HP pathology in 40% of patients and HP with associated pathologies in 60% of cases without significant fibrotic changes. Conclusion HP is more common in women and middle ages. Histopathological findings revealed no significant fibrotic changes in most of the cases, so other mechanisms may be involved in disease progression and may affect treatment response.

Objective To quantify the potential decline in dynamic lung volumes following coronavirus disease 2019 (COVID-19) in the general population. Methods A prospective matched cohort study of adult Copenhagen General Population Study (CGPS) participants with a pre-pandemic spirometry available. CGPS individuals with a positive SARS-CoV-2 polymerase chain reaction (PCR) test performed a repeat spirometry, a questionnaire regarding respiratory symptoms and a diffusing capacity test for carbon monoxide. A matched uninfected CGPS control sample was used, and simple regression and linear mixed effect models were computed to study lung function decline. Results A total of 606 were included. 92/107 (85.9%) of individuals with a positive SARS-CoV-2 PCR test experienced COVID-19 symptoms and 12 (11.2%) were hospitalized. Spirometry was performed at a median (interquartile range) of 5.6 (3.9-12.8) months after positive SARS-CoV-2 PCR test. COVID-19 was associated with an adjusted 7.3 mL (95%CI: 0.3-14.3) and 22.6 mL (95%CI: 13.1-32.0) steeper decline in annual FEV1 and FVC or a total of 113.8 and 301.3 ml lower FEV1 and FVC from baseline to follow up. Results were robust in analyses restricted to individuals not requiring hospitalization. Conclusion COVID-19 related decline of dynamic lung volumes in the general population not requiring hospitalization were small but measurable.

Sports performance in athletes can be limited by respiratory factors, so it is understandable to propose that inspiratory muscle training (IMT) can improve respiratory function and exercise performance. Power-Breathe® (PwB) is a sectorized respiratory muscle training tool that uses a resistive load to train IMT. There is currently a growing interest in respiratory muscle training, so we set out to systematically assess the effects of IMT with PwB on respiratory parameters and athletic performance in physically active, healthy adults. Based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline, the Cochrane and PEDro scales to assess methodological quality, effect size using the Rosenthal formula, and the Cochrane tool for estimation of risk of bias, studies searchable in Medline, Web of Science, and Cochrane. In addition, for the performance of the meta-analysis, the documentation and quantification of the heterogeneity in each meta-analysis were directed through the Cochran’s Q test and the I2 statistic; in addition, a publication bias analysis was performed using funnel plots. Of the total of 241 studies identified in the search, 11 studies for the systematic review and nine for the meta-analysis met the exclusion and/or inclusion criteria. IMT, with PwB, showed significant improvements in maximal inspiratory pressure (MIP) and substantial improvements in forced vital capacity (FVC) in the meta-analysis results. Also, sports performance was significantly increased by IMT with PwB. In conclusion, the use of PwB is an IMT tool that improves respiratory and sports performance.

BACKGROUND: Studies 4658-201/202 (201/202) evaluated treatment effects of eteplirsen over 4 years in patients with Duchenne muscular dystrophy and confirmed exon-51 amenable genetic mutations. Chart review Study 4658-405 (405) further followed these patients while receiving eteplirsen during usual clinical care. OBJECTIVE: To compare long-term clinical outcomes of eteplirsen-treated patients from Studies 201/202/405 with those of external controls. METHODS: Median total follow-up time was approximately 6 years of eteplirsen treatment. Outcomes included loss of ambulation (LOA) and percent-predicted forced vital capacity (FVC%p). Time to LOA was compared between eteplirsen-treated patients and standard of care (SOC) external controls and was measured from eteplirsen initiation in 201/202 or, in the SOC group, from the first study visit. Comparisons were conducted using univariate Kaplan-Meier analyses and log-rank tests, and multivariate Cox proportional hazards models with regression adjustment for baseline characteristics. Annual change in FVC%p was compared between eteplirsen-treated patients and natural history study patients using linear mixed models with repeated measures. RESULTS: Data were included from all 12 patients in Studies 201/202 and the 10 patients with available data from 405. Median age at LOA was 15.16 years. Eteplirsen-treated patients experienced a statistically significant longer median time to LOA by 2.09 years (5.09 vs. 3.00 years, p

Background: The impact of heavy metals on pulmonary function among young adults has been scarcely studied, especially by a longitudinal cohort study. Methods: We prospectively enrolled 974 young adults (aged 20–45 years) during 2017–2019 and measured pulmonary function and urinary heavy metals, including manganese, copper, chromium, iron, nickel, zinc, cadmium, and lead. Among them, 461 participants had examination of the same urinary heavy metals during 2006–2008, which could be used as a cohort for long-term effect of urinary metals on pulmonary function. Results: In the 974 enrolled participants, urinary heavy metals were within normal range. The urinary manganese level was the only significant factor for the observed/predicted ratios of forced vital capacity (FVC %)(β coefficient: −1.217, p = 0.030), forced expiratory volume in one second (FEV1%)(β: −1.664, p

Adults with obesity exhibit a restrictive pattern, whereas children with obesity exhibit an obstructive pattern. However, the transition process remains unclear. We performed a systematic search for studies reporting on body mass index and pulmonary function in children. The main outcomes were forced expiratory volume in 1 s (FEV1 ), forced vital capacity (FVC), and their ratio (FEV1 /FVC). We compared individuals with overweight or with obesity with individuals with normal weight. Random-effects models were used to calculate pooled estimates. A total of 17 studies were included. Individuals with obesity had a lower FEV1 /FVC ratio (mean difference [MD] = -3.61%; 95% confidence interval [CI] = -4.58%, -2.64%) and a higher percent-predicted FVC (MD = 3.33%; 95% CI = 0.79%, 5.88%) than those with normal weight. Obesity impaired pulmonary function in the obstructive pattern during childhood to young adulthood, and the maximum obstruction was observed at the age of 16 years in boys and 20 years in girls. The effects attenuated at approximately 30 years and then shifted to the restrictive pattern after 35 years of age in men and 40 years in women. The effects of obesity on pulmonary function change from the obstructive pattern in childhood to the restrictive pattern in adulthood.

Background: Asthma-chronic obstructive pulmonary disease (COPD) overlap (ACO) represents the confluence of bronchial airway hyperreactivity and chronic airflow limitation and has been described as leading to worse lung function and quality of life than found with either singular disease process. Objective: We aimed to describe the prevalence and risk factors for ACO among adults across 6 low- and middle-income countries (LMICs). Methods: We compiled cross-sectional data for 11,923 participants aged 35 to 92 years from 4 population-based studies in 12 settings. We defined COPD as postbronchodilator FEV 1 /forced vital capacity ratio below the lower limit of normal, asthma as wheeze or medication use in 12 months or self-reported physician diagnosis, and ACO as having both. Results: The prevalence of ACO was 3.8% (0% in rural Puno, Peru, to 7.8% in Matlab, Bangladesh). The odds of having ACO were higher with household exposure to biomass fuel smoke (odds ratio [OR], 1.48; 95% CI, 0.98-2.23), smoking tobacco (OR, 1.28 per 10 pack-years; 95% CI, 1.22-1.34), and having primary or less education (OR, 1.35; 95% CI, 1.07-1.70) as compared to nonobstructed nonasthma individuals. ACO was associated with severe obstruction (FEV 1 %

Idiopathic pulmonary fibrosis (IPF) is a chronic lung disease with great variability in disease severity and rate of progression. The need for a reliable, sensitive, and objective biomarker to track disease progression and response to therapy remains a great challenge in IPF clinical trials. Over the past decade, quantitative computed tomography (QCT) has emerged as an area of intensive research to address this need. We have gathered a group of pulmonologists, radiologists and scientists with expertise in this area to define the current status and future promise of this imaging technique in the evaluation and management of IPF. In this Pulmonary Perspective, we review the development and validation of six computer-based QCT methods and offer insight into the optimal use of an imaging-based biomarker as a tool for prognostication, prediction of response to therapy, and potential surrogate endpoint in future therapeutic trials.

Background Clinical course of pleuroparenchymal fibroelastosis (PPFE) shows considerable variation among patients, but there is no established prognostic prediction model for PPFE. Methods The prediction model was developed using retrospective data from two cohorts: our single-center cohort and a nationwide multicenter cohort involving 21 institutions. Cox regression analyses were used to identify prognostic factors. The total score was defined as the weighted sum of values for the selected variables. The performance of the prediction models was evaluated by Harrell’s concordance index (C-index). We also examined the usefulness of the gender-age-physiology (GAP) model for predicting the prognosis of PPFE patients. Results We examined 104 patients with PPFE (52 cases from each cohort). In a multivariate Cox analysis, a lower forced vital capacity (FVC [defined as FVC 550 U/mL, HR, 2.56) were significantly associated with a poor prognosis. The total score was calculated as 1 × (FVC, 550 U/mL). PPFE patients were divided into three groups based on the prognostic score: stage I (0–1 points), stage II (2 points), and stage III (3–4 points). The survival rates were significantly different in each stage. The GAP stage was significantly associated with the prognosis of PPFE, but no difference was found between moderate (stage II) and severe (stage III) disease. Our new model for PPFE patients (PPFE Prognosis Score) showed better performance in the prediction of mortality in comparison to the GAP model (C-index of 0.713 vs. 0.649). Conclusions Our new model for PPFE patients could be useful for predicting their prognosis.

Purpose: Poor forced vital capacity (FVC) effort has been considered to be the main reason for FVC reduction by the ATS/ERS guideline; however, this has rarely been mentioned in previous studies. The present study aims to determine whether reduced FVC in asthmatic children is correlated to poor FVC effort.Methods: A total of 209 asthmatic children within 5–13 years old were included and divided into reduced FVC (“restricted,” n = 66) and typical obstruction group (“obstructed,” n = 143). Forced expiratory flows before and after bronchodilation were recorded in asthmatic children. The differences in clinical characteristics, spirometric results, FVC effort, and bronchodilator response were compared between two groups. Exhalation time (ET) was divided into effective ET (ETe) and plateau ET (ETp) by the start point of exhalation plateau on the time-volume curve. FVC effort was assessed by ET, ETp, and back extrapolated volume (EV)/FVC (%).Results: Asthmatic children in the restricted group had significantly higher slow vital capacity (SVC)/FVC (%), higher EV/FVC (%), shorter ET, shorter ETe, and longer ETp, when compared with those with obstructed. In the obstructed group, ET (r = 0.201, P = 0.016) and ETe (r = 0.496, P < 0.001) positively correlated with FVC, and ETp (r = −0.224, P = 0.007) negatively correlated with FVC. In the restricted group, FVC positively correlated with ETe (r = 0.350, P = 0.004) but not ET and ETp. FVC z-score significantly correlated with total IgE (n = 51, r = −0.349, P = 0.012) and with FEF25−75% z-score (n = 66, r = 0.531, P < 0.001) in the restricted group. The further logistic regression revealed that the risk of restricted increased by 1.12 (95% CI, 1.04–1.22, P = 0.005) with every 1% increase in %ΔFVC. In subjects with restricted and bronchodilation tests, %ΔFVC was significantly associated with FeNO (n = 29, r = 0.386, P = 0.039), FEF25−75% z-score (n = 29, r = −0.472, P = 0.010), and SVC/FVC (%) (n = 19, r = 0.477, P = 0.039) but not with EV/FVC (%), ET, ETe, or ETp (P > 0.05).Conclusion: These findings suggested that “poor FVC effort” does not account for the FVC reduction in asthmatic children. Short ET and high SVC/FVC (%) are characteristics of reduced FVC.

Objective: To evaluate how Amyotrophic Lateral Sclerosis (ALS) patients��� mortality rates change, based on different levels of forced vital capacity (FVC) and disease duration, providing a scheme of mortality rates of a real population of ALS patients to improve the design of future RCTs. Methods: One random spirometry for each ALS patient was selected during four time intervals from disease onset: (1) ���12 months; (2) ���18 months; (3) ���24 months; (4) ���36 months. Date of spirometry corresponded to date of trial entry, while time interval onset-spirometry to disease duration at enrollment. Mortality rates from inclusion were computed at different time intervals. Based on progression rates, patients were stratified in slow, intermediate and fast progressors. Survival from recruitment was calculated depending on FVC, disease duration and progression rate. Results: We included 659 patients in group 1, 888 in group 2, 1019 in group 3 and 1102 in group 4. Mortality rates were higher in each group at reducing the FVC cutoff used for recruitment (p p Conclusions: This is a simple model for setting eligibility criteria, based on mortality rates of patients depending on FVC and disease duration, to select the best population for RCTs, tailored to trials��� primary endpoints and duration.

Background TAS-115, a novel multi-kinase inhibitor, demonstrated antifibrotic effects in vitro and in vivo. Methods This is an open-label, intra-patient comparison, exploratory phase 2 study of TAS-115 to evaluate the efficacy and safety in idiopathic pulmonary fibrosis (IPF) patients when orally administered at 200 mg once daily on a 5-day on and 2-day off regimen for 13 weeks. This study consists of three cohorts: previously treated with pirfenidone (Cohort P, n = 20), with nintedanib (Cohort N, n = 20), and treatment naïve (Cohort U, n = 10). Male or female patients aged ≥40 to, Highlights • A novel multi-kinase inhibitor TAS-115 demonstrated antifibrotic effects in vivo. • This is a study design of TAS-115 in patients with idiopathic pulmonary fibrosis. • Patients with disease progression despite treatment with medications were enrolled. • Efficacy of TAS-115 will be evaluated using intra-patient change in %FVC.

Background Pompe disease is a rare, progressive metabolic myopathy. The aim of this study is to investigate the associations of physical outcomes with patient-reported outcome measures (PROMs) in late-onset Pompe disease. Methods We included 121 Dutch adult patients with Pompe disease. Physical outcomes comprised muscle strength (manual muscle testing using Medical Research Council [MRC] grading, hand-held dynamometry [HHD]), walking ability (6-min walk test [6MWT]), and pulmonary function (forced vital capacity [FVC] in upright and supine positions). PROMs comprised quality of life (Short Form 36 health survey [SF-36]), participation (Rotterdam Handicap Scale [RHS]) and daily-life activities (Rasch-Built Pompe-Specific Activity [R-PAct] Scale). Analyses were cross-sectional: the time-point before, and closest to, start of Enzyme Replacement Therapy was chosen. Associations between PROMs and physical outcomes were investigated using linear regression models. Results RHS and R-PAct scores were better in patients with higher FVC supine and upright, HHD, MRC and 6MWT scores, accounting for the effect of sex, disease duration, use of wheelchair and ventilator support. While the SF-36 Physical Component Summary (PCS) was correlated positively with FVC upright, HHD, MRC and 6MWT scores, there was no significant relationship between the SF-36 Mental Component Summary (MCS) and any of the physical outcomes. Conclusions Participation, daily-life activities, and the physical component of quality of life of adult Pompe patients are positively correlated to physical outcomes. This work serves as a first step towards assessing how changes over time in physical outcomes are related to changes in PROMs, and to define the minimal change in physical outcomes required to make an important difference for the patient.

Maximal inspiratory pressure (MIP) and maximal expiratory pressure (MEP) are measures of respiratory muscle strength and may be more sensitive in detecting early respiratory muscle impairment compared with spirometry. Respiratory muscle strength is a proven conjecturer of many diseases like muscular dystrophy, neuromuscular disease, amyotrophic lateral sclerosis and spinal muscular atrophy. Maximal inspiratory pressure is gaining interest as a test to improvise impaired respiratory muscle strength of COVID-19 patients following infection. The primary aim of this study is to discuss the potential role of respiratory muscle performance followed by coronavirus infection. The sensitivity and specificity of MIP and MEP was estimated on patients suffering with chronic lung disease. This study proposes a hypothesis that aims to screen for respiratory muscle impairment in patients with dyspnea or characteristics associated with increased risk of severe respiratory complaints.

Hypovitaminosis D has been linked to several non-bone diseases. Relation between 25-hydroxyvitamin D [25(OH)D] and lung function and lung diseases has received little attention at the global level. Cross-sectional data from three National Health and Nutrition Examination Surveys, 2007–2008, 2009–2010, and 2011–2012 were used to investigate the relationship between serum 25(OH)D concentrations and lung function makers [forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1)] and lung diseases (asthma, emphysema, and chronic bronchitis) with multivariate regression models (n = 11,983; men, 6,010; women, 5,973). Serum 25(OH)D concentrations were directly associated with FVC and FEV1 (P for trend

Background Handgrip strength (HGS) has been widely studied in clinical and epidemiological settings, but the relationship between HGS and pulmonary function is still controversial. This study analysed pulmonary function and HGS stratified by sex and age in a healthy Chinese Han population, as well as the associations between HGS and pulmonary function parameters. Methods HGS was measured by a Jamar dynamometer and pulmonary function was tested using a portable spirometer. Frequencies and variables are presented as percentages and means ± standard deviations, respectively. Chi-square tests were used for comparisons of categorical variables, and Student’s t-tests or Mann–Whitney U-tests were used for continuous variables. Pearson’s correlation coefficients were used to analyse the normally distributed variables, and Spearman correlation coefficients were used to analyse the non-normally distributed variables. Multivariate linear regression models were employed to explore the relationships between HGS and parameters of pulmonary function. The statistical significance was set at p Results Cross-sectional data were available for 1519 subjects (59.0% females, 57.9 ± 13.3 years old). Males had higher average HGS than females (40.2 vs. 25.0 kg, p p p Conclusions Both pulmonary function and HGS were inversely correlated with age, and better pulmonary function was associated with greater handgrip strength.

Background Whether increased life expectancy is accompanied by increased functional capacity in older people at specific ages is unclear. We compared similar validated measures of maximal physical performance in 2 population-based older cohorts born and assessed 28 years apart. Method Participants in the first cohort were born in 1910 and 1914 and were assessed at age 75 and 80 years, respectively (N = 500, participation rate 77%). Participants in the second cohort were born in 1938 or 1939 and 1942 or 1943 and were assessed at age 75 and 80 years, respectively (N = 726, participation rate 40%). Participants were recruited using a population register and all community-dwelling persons in the target area were eligible. Both cohorts were interviewed at home and were examined at the research center with identical protocols. Maximal walking speed, maximal isometric grip and knee extension strength, forced vital capacity (FVC) and forced expiratory volume in 1 second (FEV1) were assessed. Data on non-participation were systematically collected. Results Walking speed was on average 0.2–0.4 m/s faster in the later than earlier cohort. In grip strength, the improvements were 5%–25%, and in knee extension strength 20%–47%. In FVC, the improvements were 14–21% and in FEV1, 0–14%. Conclusions The later cohort showed markedly and meaningfully higher results in the maximal functional capacity tests, suggesting that currently 75- and 80-year-old people in Finland are living to older ages nowadays with better physical functioning.

BACKGROUND: Our aim in this study was to compare the blood gas changes, the malondialdehyde (MDA) and endogenous antiox-idant glutathione (GSH) levels in blood and lung tissues after ischemia/reperfusion, the histopathological damage in lung tissue in rats provided respiratory support with mechanical ventilation after translaryngeal intubation and tracheostomy. METHODS: Group 1 rats were provided mechanical ventilator support after translaryngeal intubation, Group 2 mechanical ventilator support after tracheostomy, and Group 3 was the control group where rats were only anesthetized. Three groups were compared for blood gas changes, MDA, GSH, and histopathological changes. RESULTS: Blood gas evaluation showed a more marked increase in pO2 values and decline in pCO2 values in Group 2 than Group 1 (p0.05). In terms of histopathological scoring, the damage score in Group 1 was higher than in Group 2 (p

Study Design: A systematic review and meta-analysis. Objectives: Pulmonary dysfunction is often advocated among the indications for surgical correction of adolescent idiopathic scoliosis (AIS). Previous studies have discussed the effect of scoliosis correction on respiratory function without reaching a definitive conclusion: Some showed that the respiratory function can improve after scoliosis surgery without defining the precise role of anterior, posterior, and combined approaches on this improvement; furthermore, the majority of these studies did not take normal growth into account. As a result, the role of surgery remains to be clarified. The object of the present study was to synthesize the current knowledge regarding changes in respiratory function after posterior corrective surgery for AIS. Methods: A comprehensive systematic search was performed to identify all relevant studies in the following electronic databases: MEDLINE, EMBASE, CINAHL (EBSCO). We focused on the studies (1) that discussed posterior fusion surgery for AIS without thoracoplasty, (2) that discussed comparisons of pre- and postoperative percent-predicted values of forced vital capacity (%FVC) or forced expiratory volume (%FEV), and (3) with minimum 2-year follow-up. Forest plots were depicted and Z value was calculated as a test for overall effect. Results: Ten studies (6 prospective and 4 retrospective studies) met our inclusion criteria. The overall effect showed that there was no significant difference in %FVC or %FEV between pre- and postoperative measurements (very low evidence). Conclusions: Posterior correction surgery for mild to moderate AIS patients showed no significant improvement of postoperative respiratory function measured by relative, percent-predicted values at minimum 2-year follow-up.

Rationale: A positive bronchodilator response (BDR) according to American Thoracic Society/European Respiratory Society (ATS/ERS) guidelines require both 200 ml and 12% increase in forced expiratory volume in 1 second (FEV1) or forced vital capacity (FVC) after bronchodilator inhalation. This dual criterion is insensitive in those with high or low FEV1. Objectives: To establish BDR criteria with volume or percentage FEV1 change. Methods: The largest FEV1 and FVC were identified fromthree pre- and three post-bronchodilator maneuvers in COPDGene (Genetic Epidemiology of COPD) participants. A total of 7,741 individuals with coefficient of variation less than 15% for both FEV1 and FVC formed bronchodilator categories of FEV1 response: negative (0.00% to 0.00 L to 9.00% to 16.00% to 0.16 L to 26.00% or >0.26 L). These response size categories are based on empirical limits considering average FEV1 increase of approximately 160 ml and the clinically important difference for FEV1. To compare flow and volume response characteristics, BDR-FEV1 category assignments were applied for the BDR-FVC response. Results: Twenty percent met mild and 31% met moderate or marked BDR-FEV1 criteria, whereas 12% met mild and 33% met moderate or marked BDR-FVC criteria. In contrast, only 20.6% met ATS/ERS positive criteria. Compared with the negative BDR-FEV1 category, the minimal, mild, moderate, and marked BDR-FEV1 categories were associated with greater 6-minute-walk distance and lower St. George's Respiratory Questionnaire and modified Medical Research Council dyspnea scale scores. Compared with negative BDR, moderate and marked BDR-FEV1 categories were associated with fewer exacerbations, and minimal BDR was associated with lower computed tomography airway wall thickness. Compared with the negative category, all BDR-FVC categories were associated with increasing emphysema percentage and gas trapping percentage. Moderate and marked BDR-FVC categories were associated with higher St. George's Respiratory Questionnaire scores but fewer exacerbations and lower dyspnea scores. Conclusions: BDR grading by FEV1 volume or percentage response identified subjects otherwise missed by ATS/ERS criteria. BDR grades were associated with functional exercise performance, quality of life, exacerbation frequency, dyspnea, and radiological airway measures. BDR grades in FEV1 and FVC indicate different clinical and radiological characteristics. United States Department of Health & Human Services National Institutes of Health (NIH) - USA NIH National Heart Lung & Blood Institute (NHLBI) National Center for Advancing Translational Sciences through UCLA CTSI Grant

Background: Cardiovascular comorbidities are frequent in patients with idiopathic pulmonary fibrosis (IPF), and many patients with IPF receive treatment with statins to reduce cardiovascular risk. Objectives: We investigated whether statin use at baseline was associated with differences in disease progression in placebo-treated patients or influenced the treatment effect of nintedanib in the INPULSIS® trials. Methods: Post-hoc subgroup analyses of patients receiving versus not receiving statins at baseline using pooled data from the INPULSIS® trials. Results: At baseline, 312 patients received statins and 749 did not. The annual rates of decline in forced vital capacity (FVC) in patients treated with nintedanib and placebo, respectively, were –78.9 and –187.6 mL/year in patients who received statins at baseline, and –127.9 and –237.9 mL/year in patients who did not. The effect of nintedanib was consistent across subgroups (p = 0.9590). Conclusions: In the INPULSIS® trials, there was a numerically lower FVC decline in placebo-treated patients with IPF who received statins at baseline versus those who did not. Use of statins at baseline did not influence the treatment effect of nintedanib. Prospective data are needed to assess the impact of statins on the course of IPF.

Pulmonary damage and function impairment were frequently noted in patients with diabetes mellitus (DM). However, the relationship between lung function and glycemic status in non-DM subjects was not well-known. Here, we evaluated the association of longitudinal changes of lung function parameters with longitudinal changes of glycated hemoglobin (HbA1c) in non-DM participants. The study enrolled participants without prior type 2 DM, hypertension, and chronic obstructive pulmonary disease (COPD) from the Taiwan Biobank database. Laboratory profiles and pulmonary function parameters, including forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1), were examined at baseline and follow-up. Finally, 7055 participants were selected in this study. During a mean 3.9-year follow-up, FVC and FEV1 were significantly decreased over time (both p &lt, 0.001). In the multivariable analysis, the baseline (unstandardized coefficient β = −0.032, p &lt, 0.001) and longitudinal change (unstandardized coefficient β = −0.025, p = 0.026) of FVC were negatively associated with the baseline and longitudinal change of HbA1c, respectively. Additionally, the longitudinal change of FVC was negatively associated with the risk of newly diagnosed type 2 DM (p = 0.018). During a mean 3.9-year follow-up, our present study, including participants without type 2 DM, hypertension, and COPD, demonstrated that the baseline and longitudinal change of FVC were negatively and respectively correlated with the baseline and longitudinal change of HbA1c. Furthermore, compared to those without new-onset DM, participants with new-onset DM had a more pronounced decline of FVC over time.

The lifelong infection with the human T lymphotropic virus type 1 (HTLV-1) has been associated with a variety of clinical manifestations, one of the less-explored is HTLV-1-associated pulmonary disease. Imaging of lung damage caused by the HTLV-1 hyperinflammatory cascade can be similar to sequelae from TB infection. Our study aims to describe the pulmonary lesions of HTLV-1-positive patients without past or current active TB and evaluate pulmonary function. We found that nine out of fourteen patients with no known TB disease history presented bronchiectasis, mainly found bilaterally while five presented pulmonary fibrosis. A normal pattern was found in most patients with a pulmonary functional test. Furthermore, there was no association between the PVL and the chest-CT scan findings, nor with spirometry results. However, the sample size was insufficient to conclude it.

Background A relationship between metabolic syndrome (MS) and lung disease has been observed in several cross-sectional and longitudinal studies. This syndrome has been identified as an independent risk factor for worsening respiratory symptoms and higher lung function impairment. Aim The aim of this study was to analyze the effect of MS on ventilatory pulmonary functions. Patients and methods This study included 60 participants. They were divided to two groups – group A included 45 patients with MS, and group B included 15 apparently healthy participants as a control group. All of them were subjected to the following: complete history taking and physical examination (blood pressure, BMI, and waist circumference), laboratory investigations for fasting blood glucose, lipid profile (triglyceride and high-density lipoprotein), C-reactive protein, and HbA1C, and spirometry [forced vital capacity (FVC), forced expiratory volume in first second (FEV1), and FEV1/FVC]. Results Among MS participants (n=45), 28 (63%) had the restrictive ventilatory pattern, three (6%) had the obstructive pattern, nine (20%) were normal, and five (11%) had a mixed pattern. Pulmonary functions were impaired more among MS cases. FVC% predicted of group A was 61.49±17.56%, whereas in group B it was 85.73±5.24%. FEV1% predicted of group A was 66.22±18.7%, whereas in group B it was 87.73 ±7.98%. The differences were statistically highly significant. Pulmonary function impairment was more prominent among males than among females. After examining the association between metabolic components and both FVC% predicted and FEV1% predicted, the results revealed that there was a strong linear decrease in FVC% predicted and FEV1% predicted as the number of components of MS increased. The β coefficients of FVC% predicted for those with 1, 2, 3, 4, and 5 features of MS were 0.011, −0.018, −0.023, −0.035, and −0.048 in men and 0.020, −0.029, −0.035, −0.047, and −0.068 in women, respectively. The β coefficients of FEV1% predicted for those with 1, 2, 3, 4, and 5 features of MS were 0.009, −0.015, −0.026, −0.041, and −0.051 in men and 0.004, −0.009, −0.017, −0.029, and −0.038 in women, respectively. Conclusion Pulmonary function impairment (mainly restrictive pattern) is commonly associated with MS. FVC and FEV1 are inversely associated with the accumulation of elements of MS and also associated independently with each element of MS, especially waist circumference.

Shoichiro Yamamoto,1 Seigo Miyoshi,1 Hitoshi Katayama,1 Mikio Okazaki,2 Hisayuki Shigematsu,2 Yoshifumi Sano,2 Minoru Matsubara,3 Naohiko Hamaguchi,1 Takafumi Okura,1 Jitsuo Higaki1 1Department of Cardiology, Pulmonology, Hypertension, and Nephrology, 2Department of Cardiovascular and Thoracic Surgery, Ehime University Graduate School of Medicine, Toon, 3Department of Internal Medicine, Sumitomo Besshi Hospital, Niihama, Japan Purpose: Spirometry is sometimes difficult to perform in elderly patients and in those with severe respiratory distress. The forced-oscillation technique (FOT) is a simple and noninvasive method of measuring respiratory impedance. The aim of this study was to determine if FOT data reflect spirometric indices.Patients and methods: Patients underwent both FOT and spirometry procedures prior to inclusion in development (n=1,089) and validation (n=552) studies. Multivariate linear regression analysis was performed to identify FOT parameters predictive of vital capacity (VC), forced VC (FVC), and forced expiratory volume in 1 second (FEV1). A regression equation was used to calculate estimated VC, FVC, and FEV1. We then determined whether the estimated data reflected spirometric indices. Agreement between actual and estimated spirometry data was assessed by Bland–Altman analysis.Results: Significant correlations were observed between actual and estimated VC, FVC, and FEV1 values (all r>0.8 and P0.8 and P

Introduction: Bilateral breast reduction surgery is the surgical treatment of bilateral breast hypertrophy. This is one of the most common breast surgery requested by women, and performed by plastic surgeons. The reasons that patients want this surgery are to re-size sagging breasts aesthetically, and to get rid of somatic symptoms such as shoulder, chest, back, and neck pain. We believe that the objective positive effects of breast reduction surgery exist beside aesthetic. In our study, our aim is to elicit positive effects of surgery on lungs, if there are, by making pulmonary function test and carbon monoxide diffusion test before surgery and after 6 months of surgery. Materials and Methods: Thirty patients agreed to participate in the study. Study is completed with 19 patients. Pulmonary function test and carbon monoxide diffusion test were made to all patients in preoperative and 6 months of postoperative period. Lung roentgenogram of all patients was performed and height, weight, body mass index were measured. Saturation level was measured. Results: There was a meaningful increase in FEV1 and FVC values in the postoperative period in comparison with pulmonary function test performed in preoperative period. DLCO in postoperative period decreased meaningfully as compared to the preoperative period. Conclusion: Breast reduction surgery seems to have positive effects on pulmonary function test values and relaxes patients clinically. Patients with big breasts should be evaluated from this perspective if they apply chest diseases clinic with shortness of breath. © 2017, Ankara University. All rights reserved.

The basis for the pathogenesis of systemic sclerosis (SS) is immune disorders that initiate inflammation, as well as vasculopathy with obvious microcirculatory disturbances, and generalized fibrosis. In SS, lung injury is due to an arterial lesion and/or a fibrotic process in the lung parenchyma and occurs as two major syndromes that are rarely concurrent in one patient; these are pulmonary arterial hypertension and interstitial lung disease (ILD). In SS, lung injury negatively affects the prognosis and ranks first among the causes of death. The review focuses on ILD, the most common injury of the respiratory tract in SS, which is detectable in 80% of patients, as evidenced by multislice spiral computed tomography (MSCT) of the chest. The histological manifestations are similar to those of idiopathic ILDs, but the histological type does not determine the prognosis. The course of ILD in SS is relatively benign, often subclinical. A severe progressive lesion develops only in 10–15% of cases. Clinically significant changes in the lung parenchyma develop early, within the first 3–5 years of the disease. Pulmonary functional tests show that relatively preserved and stable forced vital capacity is long recorded in the majority of patients, but the diffusing capacity of the lung is reduced in 70–80% of the patients. The values of pulmonary tests during the first examination are of prognostic value; the lower than normal they are, the worse the prognosis. Chest MSCT should be carried out in all patients with newly diagnosed SS, as the quantitative (prevalence) and qualitative (frosted glass, honeycomb lung) indicators affect the determination of therapy policy. ILD treatment is performed only in patients with obvious signs of progression, which are determined from the time course of changes in the decrease of values of pulmonary functional tests. Immunosuppressants, cyclophosphamide being the drug of choice, are used to treat ILD; biological agents, tocilizumab in particular, are currently being tested.

Objectives: To find out the association of weight, height and age with spirometry variables and to generate a regression equation by taking weight as an independent variable beside age and height among children and adolescents of Karachi. Methods: A modified form of ISSAC questionnaire was used. The spirometry variables recorded were Forced vital capacity (FVC), Forced expiratory volume in 1 second (FEV1), FEV1/FVC, Peak expiratory flow rate (PEF), Forced expiratory flow between 25% and 75% expired volume (FEF25-75). A person’s correlation coefficient among boys and girls were calculated for all spirometry variable considering age, height and weight as independent variables. The linear regression models were calculated. Results: The results reported a linear correlation of lung function variables with all three independent variables (i.e. p-value = 0.000), in which age and height manifested a strong positive correlation while weight reported a moderately significant correlation. All spirometry variables such as FVC, FEV1, PEF and FEF25-75 reported a significant coefficient of dependency and coefficient of correlation individually with age, height and weight. Conclusion: It is concluded that beside age, height and weight both also have significant correlation with lung volumes so these should be taken into account when using spirometry as a diagnostic test.

Context: Liuweibuqi (LWBQ) capsule has been reported to influence symptoms of patients with chronic obstructive pulmonary disease (COPD); however, specific function of LWBQ capsules in COPD with lung-qi deficiency syndrome remains elusive. Objective: This study investigates effect of LWBQ capsules on STAT4/STAT6 and MMP-9/TIMP-1 expression and pulmonary function in stable COPD with lung-qi deficiency syndrome. Materials and methods: Totally, 429 patients diagnosed with stable COPD and lung-qi deficiency syndrome were treated with starch capsules (each time for 9 capsules), or different doses: low (each dose for 8 capsules and 1 LWBQ capsules), medium (each time for 6 capsules and 3 LWBQ capsules), or high (each time for 9 LWBQ capsules) of LWBQ capsules for 30 days, 3 times a day. Forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), FEV1/FVC% and DLco%pred were evaluated by pulmonary function meter. STAT4/STAT6 and MMP-9/TIMP-1 expression was assessed by RT-qPCR and western blot analysis, and serum concentrations of IL-4, IFN-γ and IL-6 by ELISA. Results: Spearman rank correlation analysis and ROC curve showed that STAT4/STAT6 and MMP-9/TIMP-1 affected pulmonary functions and curative effect of stable COPD with lung-qi deficiency syndrome. After LWBQ capsule treatment, FEV1, FVC, FEV1/FVC% and DLco%pred elevated; STAT4/STAT6, MMP-9/TIMP-1, IFN-γ and IL-6 expression declined whereas IL-4 expression increased (p

Chronic obstructive pulmonary disease or COPD is one of the conditions that physicians frequently see in both the hospital and outpatient setting. In order to improve diagnostic and treatment outcomes, the Global Strategy for the Diagnosis, Management and Prevention of COPD, the Global Initiative for Chronic Obstructive Lung Disease (GOLD) was created in 2001. Every year, a new report is generated based on an analysis of published studies which attempts to improve the way physicians handle COPD. GOLD reports are considered to be essential evidence-based reference tools for the implementation of effective management plans, and represent the current best practices for the care of patients with COPD. The 2017 report greatly revised the guidelines and added a few components that changed the system of COPD diagnosis and treatment. This review article addresses those changes, explains the current guidelines, and draws attention to areas that still require improvement.

Background An incentive spirometer (IS) is a mechanical device that promotes lung expansion. It is commonly used to prevent postoperative lung atelectasis and decrease pulmonary complications after cardiac, lung, or abdominal surgery. This study explored its effect on lung function and pulmonary complication rates in patients with rib fractures. Methods Between June 2014 and May 2017, 50 adult patients with traumatic rib fractures were prospectively investigated. Patients who were unconscious, had a history of chronic obstructive pulmonary disease or asthma, or an Injury Severity Score (ISS) ≥ 16 were excluded. Patients were randomly divided into a study group (n = 24), who underwent IS therapy, and a control group (n = 26). All patients received the same analgesic protocol. Chest X-rays and pulmonary function tests (PFTs) were performed on the 5th and 7th days after trauma. Results The groups were considered demographically homogeneous. The mean age was 55.2 years and 68% were male. Mean pretreatment ISSs and mean number of ribs fractured were not significantly different (8.23 vs. 8.08 and 4 vs. 4, respectively). Of 50 patients, 28 (56%) developed pulmonary complications, which were more prevalent in the control group (80.7% vs. 29.2%; p = 0.001). Altogether, 25 patients had delayed hemothorax, which was more prevalent in the control group (69.2% vs. 29.2%; p = 0.005). Two patients in the control group developed atelectasis, one patient developed pneumothorax, and five patients required thoracostomy. PFT results showed decreased forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1) in the control group. Comparing pre- and posttreatment FVC and FEV1, the study group had significantly greater improvements (p Conclusions In conclusion, the use of an IS reduced pulmonary complications and improved PFT results in patients with rib fractures. The IS is a cost-effective device for patients with rib fractures and its use has clinical benefits without harmful effects. Trial registration ClinicalTrials.gov, NCT04006587. Registered on 3 July 2019.

Objective: Spirometry is commonly used as screening tool for respiratory insufficiency in neuromuscular diseases. Despite the well-known effects of reference standards on spirometric outcomes, its standardization is overlooked in current guidelines. We aim to illustrate the effect of spirometric reference values on prognostication, medical decision-making, and trial eligibility in the applied setting of amyotrophic lateral sclerosis (ALS). Methods: We selected 4,651 patients with 32,022 FVC measurements from the PRO-ACT dataset. The FVC estimates were standardized according to five reference standards: Knudson '76, Knudson '83, ECSC, NHANES III, and GLI-2012. (Generalized) linear mixed-effects and Cox proportional hazard models were used to evaluate longitudinal patterns and time-to-event outcomes. Results: The mean population %predicted FVC varied between 78.5% (95% CI 78.0-79.1) and 88.5% (95% CI 87.9-89.1). The unstandardized liters provided the worst fit on the survival data (AIC 20573, c-index 0.760), whereas the GLI provided the best fit (AIC 20374, c-index 0.780, p

Background Pirfenidone suppresses the decline of forced vital capacity (FVC) in patients with idiopathic pulmonary fibrosis (IPF). However, IPF progresses in some patients despite treatment. We analyzed patients with meaningful FVC declines during pirfenidone treatment and explored the factors predictive of disease progression after FVC decline. Methods This study was a retrospective, multicenter, observational study conducted by the Okayama Respiratory Disease Study Group. We defined initial decline in %FVC as 5% or greater per 6-month period during pirfenidone treatment. IPF patients who were treated with pirfenidone and experienced an initial decline from December 2008 to September 2017 were enrolled. Results We analyzed 21 patients with IPF. After the initial decline, 4 (19.0%) patients showed improvement in disease, 11 (52.4%) showed stable disease, and 6 (28.6%) showed progressive disease. There was no significant correlation between %FVC reduction on initial decline and subsequent %FVC change (p = 0.475). Deterioration of high-resolution computed tomography (HRCT) findings on initial decline was observed significantly more often in the progressive versus improved/stable disease groups (100% vs 20.0%, p = 0.009). Conclusions We revealed that deterioration of HRCT findings may predict disease progression after the initial decline in %FVC in IPF patients treated with pirfenidone.

Background: Adherence to inhaled drugs is linked to patients’ satisfaction with their device, and an incorrect use can negatively affect the outcomes of asthma treatment. We speculated that this is particularly true in elderly asthmatic subjects. Aim: We performed a national pre-post interventional multicentre study, enrolling moderate-to-severe asthmatic subjects aged ≥65 ​years treated with fixed inhaled combination drugs by dry powder inhaler (DPI) or pressurized metered dose inhaler (pMDI). Adherence and critical errors were evaluated by means of validated questionnaires at first visit (V1) and after 3–6 months (V2). At V1, subjects underwent intensive training on the correct use of their device by physical demonstration. Results: A total of 411 asthmatics (F/M: 238/173, mean age±SD: 72 ​± ​5 ​years) participated to the study. At V1, 50% of the study subjects showed an Asthma Control Test (ACT) score ≤19 despite GINA step 3 and 4 treatment, and 40% had experienced at least one severe asthma exacerbation in the previous year. Poor adherence to treatment was recorded in 43% of subjects, and at least one error in using the device was registered in 56% of subjects. At V2, available for 318 patients, both the percentage of individuals with poor adherence and with at least one critical error significantly decreased (from 46% to 25%, and from 49% to 25%, respectively; p ​

Introduction Forced vital capacity is the only registrational endpoint in idiopathic pulmonary fibrosis clinical trials. As most new treatments will be administered on top of standard of care, estimating treatment response will become more challenging. We developed a simulation model to quantify variability associated with forced vital capacity decline. Methods The model is based on publicly available clinical trial summary and home spirometry data. A single, illustrative trial setting is reported. Model assumptions are 400 subjects randomised 1:1 to investigational drug or placebo over 52 weeks, 50% of each group receiving standard of care (all-comer population), and a 90-mL treatment difference in annual forced vital capacity decline. Longitudinal profiles were simulated and the impact of varying clinical scenarios evaluated. Results Power to detect a significant treatment difference was 87–97%, depending on the analysis method. Repeated measures analysis generally outperformed analysis of covariance and mixed linear models, particularly with missing data (as simulated data were non-linear). A 15% yearly random dropout rate led to 0.6–5% power loss. Forced vital capacity decline-related dropout introduced greater power loss (up to 12%), as did subjects starting/stopping standard of care or investigational drug. Power was substantially lower for a 26-week trial due to the smaller assumed treatment effect at week 26 (sample size would need doubling to reach a power similar to that of a 52-week trial). Conclusions Our model quantifies forced vital capacity decline and associated variability, with all the caveats of background therapy, permitting robust power calculations to inform future idiopathic pulmonary fibrosis clinical trial design. Funding Galapagos NV (Mechelen, Belgium). Electronic supplementary material The online version of this article (10.1007/s12325-019-01093-3) contains supplementary material, which is available to authorized users.

Background: The full-scale airway network (FAN) flow model shows excellent agreement with limited functional imaging data but requires further validation prior to clinical use. Purpose: To validate the ventilation distributions computed with the FAN flow model with xenon ventilation from xenon-enhanced dual-energy (DE) CT in participants with chronic obstructive pulmonary disease (COPD). Materials and Methods: in this prospective study, the FAN model extracted structural data from xenon-enhanced DE CT images of men with COPD scanned between June 2012 and July 2013 to compute gas ventilation dynamics. The ventilation distributions on the middle cross-section plane, percentage lobar ventilation, and ventilation heterogeneity quantified by the coefficient of variation (CV) were compared between xenon-enhanced DE CT imaging and the FAN model. The relationship between the ventilation parameters with the densitometry and pulmonary function test results was demonstrated. The agreements and correlations between the parameters were measured using the concordance correlation coefficient and the Pearson correlation coefficient. Results: Twenty-two men with COPD (mean age, 67 years +/- 7 [standard deviation]) were evaluated. The percentage lobar ventilation computed with FAN showed a strong positive correlation with xenon-enhanced DE CT data (r = 0.7, P < .001). Ninety-five percent of lobar ventilation CV differences lay within 95% confidence intervals. Correlations of the percentage lobar ventilation were negative for percentage emphysema (xenon-enhanced DE CT: r = -0.38, P < .001; FAN: r = -0.23, P = .02) but were positive for percentage normal tissue volume (xenon-enhanced DE CT: r = 0.78, P < .001; FAN: r = 0.45, P < .001). Lung CVs of FAN revealed negative correlations with the spirometry results (CVFAN vs percentage predicted forced expiratory volume in 1 second: r = -0.75, P < .001; CVFAN vs ratio of forced expiratory volume in 1 second to forced vital capacity: r = -0.67, P < .001). Conclusion: The full-scale airway network modeled lobar ventilation in patients with chronic obstructive pulmonary disease correlated with the xenon-enhanced dual-energy CT imaging data. (C) RSNA, 2020, Cancer Research UKCancer Research UK [C5255]; Engineering and Physical Sciences Research CouncilUK Research & Innovation (UKRI)Engineering & Physical Sciences Research Council (EPSRC) [A16466]; NIHR Oxford Biomedical Research CentreNational Institute for Health Research (NIHR), Supported by the Cancer Research UK (grant C5255), Engineering and Physical Sciences Research Council (grant A16466), and NIHR Oxford Biomedical Research Centre.

Background: The INPULSIS trials revealed that nintedanib reduced the decline in lung function in patients with idiopathic pulmonary fibrosis. We aimed to evaluate the efficacy and safety of nintedanib in Japanese idiopathic pulmonary fibrosis patients in real-world settings. Method: Medical records of idiopathic pulmonary fibrosis patients, who received treatment with nintedanib in five institutions between July 2015 and June 2017, were reviewed. Patients with % forced vital capacity ⩾50% and % predicted diffusing capacity of the lung carbon monoxide ⩾30% were classified as the moderate group and those with more impaired lung functions as the severe group. Result: Among 158 patients analyzed, 132 (84.6%) were classified as the moderate group and 26 (15.4%) as the severe group. In the moderate group, changes in forced vital capacity in 12 months were significantly different between before and after nintedanib administration (−253 ± 163 vs −125 ± 235 mL; p = 0.0027). In contrast, changes in forced vital capacity in 12 months were not significantly changed by nintedanib treatment in the severe group (−353 ± 250 vs −112 ± 341 mL; p = 0.2374). Incidence of acute exacerbation was higher in the severe group than in the moderate group (30.8% vs 18.9%). The overall survival of the moderate and the severe groups was 17.2 and 10.1 months. Conclusion: In real-world practice, nintedanib showed comparable efficacy to those observed in previous trials. In the severe group, the efficacy of nintedanib might be limited.

Biomarkers for pulmonary manifestations in systemic lupus erythematosus (SLE) are missing. Plasma samples of nine SLE patients with known pulmonary involvement (SLEpulm) and nine SLE patients without pulmonary involvement (SLE) were tested by multiplex microarray analysis for various cyto- and chemokines. Significantly decreased lung function paramters for forced vital capacity (FVC), total lung capacity (TLC), diffusion capacity for carbon monoxide (DLCO) and diffusion of CO corrected on lung volume (KLCO) were observed in SLEpulm as compared to SLE patients. CC chemokine ligand 21 (CCL21) and interferon gamma-induced protein 10 (IP-10) levels were significantly higher in SLEpulm, than in patients without pulmonary manifestations. CCL21 correlated negatively with DLCO ( r = −0.73; p CO ( r = −0.62; p CO/KLCO changes and were associated with significant increase in CCL21 and IP-10. These chemokines might serve as potential biomarkers of lung involvement in SLE patients.

Background: The efficacy and effectiveness of nintedanib as a first-line therapy in idiopathic pulmonary fibrosis (IPF) patients have been demonstrated by clinical trials and real-life studies. Our aim was to examine the safety profile and effectiveness of nintedanib when it is utilized as a second-line treatment in subjects who have discontinued pirfenidone. Methods: The medical charts of 12 patients who were switched from pirfenidone to nintedanib were examined retrospectively. The drug’s safety was defined by the number of adverse events (AEs) that were reported; disease progression was evaluated based on the patient’s vital status and changes in forced vital capacity (FVC) at 12-month follow-up. Results: The numbers of patients experiencing AEs and of the AEs per patient in our study group didn’t significantly differ with respect to a group of 56 individuals who were taking nintedanib as a first-line therapy during the study period (5/12 vs. 22/56; p = 0.9999, and 0.00 (0.00−1.00) vs. 0.00 (0.00−3.00); p = 0.517, respectively). Two out of the 3 patients who had been switched to nintedanib due to a rapid disease progression showed stabilized FVC values. Conclusions: Nintedanib was found to have an acceptable safety profile in the majority of the IPF patients switched from pirfenidone. Prospective studies are warranted to determine if the drug can effectively delay disease progression in these patients.

Background: Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal interstitial lung disease (ILD). Currently, two antifibrotic drugs are available for reducing forced vital capacity (FVC) decline in IPF. However, many pulmonologists wait before initiating treatment, especially when IPF patients have stable disease. This study aimed to investigate the impact on survival outcome of FVC decline and a slow rate of FVC decline prior to and following treatment with these two antifibrotic drugs. Methods: Out of the 235 IPF patients treated with antifibrotic therapy that were screened, 105 cases were eligible, who then underwent physiological evaluation at 6 months prior to and following antifibrotic therapy. Clinical characteristics and prognostic outcomes were compared among groups, and prognostic factors were evaluated using a Cox proportional hazards analysis. Results: In terms of %FVC decline prior to the therapy and a slow rate of FVC decline, there was no significant difference between stable and worsened groups and responder and non-responder groups, respectively. On the other hand, in terms of %FVC decline (decline >5%) following antifibrotic therapy, the stable/improved group had significantly better prognosis than the worsened group. Prognostic analysis revealed that a stable/improved status following antifibrotic therapy [HR: 0.35 (0.15–0.87)] was significantly associated with a better prognosis. Conclusions: Concerning the FVC decline prior to and following antifibrotic therapy and a slow rate of FVC decline, only the FVC decline following the therapy is associated with a greater survival outcome. An early treatment decision may thus be beneficial for IPF. The reviews of this paper are available via the supplemental material section.

Background: Interstitial Lung Disease (ILD) is one of the major cause of morbidity and mortality in Systemic Sclerosis (SSc). The gold standard to diagnose ILD is using High Resolution Computed Tomography (HRCT) scan. HRCT scan need a lot of cost and not always available, so another diagnosing test is needed as an alternative modality to diagnose ILD. ILD is a restrictive lung disease caused by lung fibrosis which is proved by the decrease of Forced Vital Capacity (FVC) in spirometry, and followed by the increase of soluble CD40L (sCD40L) level in plasma. This sCD40L may become a potential biomarker to evaluate lung fibrosis in SSc patients. The aim of this study is to analyze the correlation of sCD40L levels with FVC score in SSc patients with restrictive lung disease.Method:This cross sectional study was enrolled by the SSc patient who has restrictive lung disease based on spirometry test, at Rheumatology outpatient clinic dr. Hasan Sadikin Hospital from May 2015 to May 2016. All subject took underwent history, physical examination, spirometry and blood test for sCD40L. Data were analyzed using Pearson correlation.Result:There were 38 subjects involved in this study, dominated bywoman (92.1%) with mean age 41(±11) years. Subjects consist of 22(57,9%) with limited SSc, 16(42,1%) with diffuse SSc patients and 33 subjects treated with DMARD. Mean sCD40L serum in this study was 6.690,3(±2.377,3) pg/mL, with no statistical difference between limited and diffuse type (p=0.154). Mean FVC score in this study was 58.2(±10,8). There was no significant correlation between sCD40L serum with FVC (r=0.058; p=0.366). There was weak correlation on DMARD naïve subject between sCD40L serum and FVC (r=0.058; p=0.366) but statistically insignificant. There was no significant correlation between sCD40L serum with mRSS (r=0,066; p=0,346).Conclusion: This study founds no correlation between sCD40L with FVC in SSc at dr. Hasan Sadikin Hospital. Keyword : sCD40L, Forced Vital Capacity, Restrictive Lung Disease, Systemic Sclerosis

ResumoJustificativaAs alterações no posicionamento corporal podem ocasionar mudanças na função respiratória e é necessário compreendê‐las, principalmente no pós‐operatório abdominal superior, já que os pacientes estão suscetíveis a complicações pulmonares pós‐operatórias.ObjetivoVerificar a capacidade vital nas posições de decúbito dorsal (cabeceira a 0° e 45°), sentado e em ortostase em pacientes no pós‐operatório de cirurgia abdominal superior.MétodosEstudo transversal, feito entre agosto de 2008 e janeiro de 2009, em um hospital na cidade de Salvador (BA). O instrumento usado para mensuração da capacidade vital (CV) foi o ventilômetro analógico e a escolha da sequência das posições seguiu uma ordem aleatória obtida a partir de sorteio das quatro posições. Os dados secundários foram colhidos nos prontuários de cada paciente.ResultadosA amostra foi composta por 30 indivíduos com idade média de 45,2±11,2 anos e IMC 20,2±1,0 kg/m2. A posição em ortostase apresentou valores maiores da CV em relação à sedestração (média das diferenças: 0,15±0,03 litros; p=0,001), ao decúbito dorsal a 45° (média das diferenças: 0,32±0,04 litros; p=0,001) e 0° (0,50±0,05 litros; p=0,001). Houve um aumento positivo entre os valores de CVF do decúbito dorsal para a postura ortostática (1,68±0,47; 1,86±0,48; 2,02±0,48 e 2,18±0,52 litros; respectivamente).ConclusãoA posição do corpo afeta os valores da CV em pacientes no pós‐operatório de cirurgia abdominal superior, com aumento nas posturas em que o tórax encontra‐se verticalizado.AbstractRationaleThe changes in body position can cause changes in lung function, it is necessary to understand them, especially in the postoperative upper abdominal surgery, since these patients are susceptible to postoperative pulmonary complications.ObjectiveTo assess the vital capacity in the supine position (head at 0° and 45°), sitting and standing positions in patients in the postoperative upper abdominal surgery.MethodsA cross‐sectional study conducted between August 2008 and January 2009 in a hospital in Salvador/BA. The instrument used to measure vital capacity (VC) was analogic spirometer, the choice of the sequence of positions followed a random order obtained from the draw of the four positions. Secondary data were collected from the medical records of each patient.ResultsThe sample consisted of 30 subjects with a mean age of 45.2±11.2 years, BMI 20.2±1.0 kg/m2. The position on orthostasis showed higher values of CV regarding standing (mean change: 0.15±0.03 liters; p=0.001), the supine to 45 (average difference: 0.32±0.04 liters; p=0.001) and 0° (0.50±0.05 liters; p=0.001). There was a positive trend between the values of FVC supine to upright posture (1.68±0.47; 1.86±0.48; 2.02±0.48 and 2.18±0.52 liters; respectively).ConclusionBody position affects the values of CV in patients in the postoperative upper abdominal surgery, increasing in postures where the chest is vertical.

Background Patients with DMD experience progressive restrictive respiratory disease and eventual respiratory failure. Standard of care guidelines command changes in disease management when forced vital capacity percent of predicted (FVC% p) falls below clinically relevant thresholds. The Phase 3 DELOS trial in patients with DMD demonstrated that idebenone reduces the loss of peak expiratory flow and FVC compared to placebo (Buyse GM, et al.; Lancet 2015; 385 : 1748-57). Objective Post-hoc analyses were conducted to assess whether treatment with idebenone could reduce the risk of patients dropping below clinically meaningful thresholds of FVC% p. Methods The DELOS trial enrolled DMD patients 10-18 years of age not using glucocorticoids to receive idebenone (N = 31) or placebo (N = 33) for 12 months. Change from baseline in FVC and FVC% p was assessed by hospital spirometry and analyzed by mixed model of repeated measures and slope analysis and proportions of patients falling below clinically meaningful thresholds of FVC% p were compared. Results The change over 1 year in FVC and FVC% p showed a consistent pattern in favor of idebenone treatment across multiple analysis methods and fewer patients in the idebenone group declined by a margin of 10% or more in FVC and FVC% p compared to placebo. There were also fewer patients in the idebenone group (15%) with a decline below FVC% p of 50% compared to the placebo group (25%) and fewer patients in the idebenone group (28%) showed a decline below FVC% p of 50% or 40% or 30% compared to the placebo group (43%). Conclusions These data added to the consistency and clinical meaningfulness of findings from the DELOS trial showing that idebenone can slow the loss of pulmonary function in patients with DMD.