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Background Idiopathic pulmonary fibrosis is a progressive fibrotic lung disease with a variable clinical trajectory. Decline in forced vital capacity (FVC) is the main indicator of progression; however, missingness prevents long-term analysis of patterns in lung function. We aimed to identify distinct clusters of lung function trajectory among patients with idiopathic pulmonary fibrosis using machine learning techniques. Methods We did a secondary analysis of longitudinal data on FVC collected from a cohort of patients with idiopathic pulmonary fibrosis from the PROFILE study; a multicentre, prospective, observational cohort study. We evaluated the imputation performance of conventional and machine learning techniques to impute missing data and then analysed the fully imputed dataset by unsupervised clustering using self-organising maps. We compared anthropometric features, genomic associations, serum biomarkers, and clinical outcomes between clusters. We also performed a replication of the analysis on data from a cohort of patients with idiopathic pulmonary fibrosis from an independent dataset, obtained from the Chicago Consortium. Findings 415 (71%) of 581 participants recruited into the PROFILE study were eligible for further analysis. An unsupervised machine learning algorithm had the lowest imputation error among tested methods, and self-organising maps identified four distinct clusters (1–4), which was confirmed by sensitivity analysis. Cluster 1 comprised 140 (34%) participants and was associated with a disease trajectory showing a linear decline in FVC over 3 years. Cluster 2 comprised 100 (24%) participants and was associated with a trajectory showing an initial improvement in FVC before subsequently decreasing. Cluster 3 comprised 113 (27%) participants and was associated with a trajectory showing an initial decline in FVC before subsequent stabilisation. Cluster 4 comprised 62 (15%) participants and was associated with a trajectory showing stable lung function. Median survival was shortest in cluster 1 (2·87 years [IQR 2·29–3·40]) and cluster 3 (2·23 years [1·75–3·84]), followed by cluster 2 (4·74 years [3·96–5·73]), and was longest in cluster 4 (5·56 years [5·18–6·62]). Baseline FEV1 to FVC ratio and concentrations of the biomarker SP-D were significantly higher in clusters 1 and 3. Similar lung function clusters with some shared anthropometric features were identified in the replication cohort. Interpretation Using a data-driven unsupervised approach, we identified four clusters of lung function trajectory with distinct clinical and biochemical features. Enriching or stratifying longitudinal spirometric data into clusters might optimise evaluation of intervention efficacy during clinical trials and patient management., National Institute for Health and Care Research, Medical Research Council, GlaxoSmithKline

Objectives Evaluation and follow-up of idiopathic pulmonary fibrosis (IPF) mainly rely on high-resolution computed tomography (HRCT) and pulmonary function tests (PFTs). The elastic registration technique can quantitatively assess lung shrinkage. We aimed to investigate the correlation between lung shrinkage and morphological and functional deterioration in IPF. Methods Patients with IPF who underwent at least two HRCT scans and PFTs were retrospectively included. Elastic registration was performed on the baseline and follow-up HRCTs to obtain deformation maps of the whole lung. Jacobian determinants were calculated from the deformation fields and after logarithm transformation, log_jac values were represented on color maps to describe morphological deterioration, and to assess the correlation between log_jac values and PFTs. Results A total of 69 patients with IPF (male 66) were included. Jacobian maps demonstrated constriction of the lung parenchyma marked at the lung base in patients who were deteriorated on visual and PFT assessment. The log_jac values were significantly reduced in the deteriorated patients compared to the stable patients. Mean log_jac values showed positive correlation with baseline percentage of predicted vital capacity (VC%) (r = 0.394, p < 0.05) and percentage of predicted forced vital capacity (FVC%) (r = 0.395, p < 0.05). Additionally, the mean log_jac values were positively correlated with pulmonary vascular volume (r = 0.438, p < 0.01) and the number of pulmonary vascular branches (r = 0.326, p < 0.01). Conclusions Elastic registration between baseline and follow-up HRCT was helpful to quantitatively assess the morphological deterioration of lung shrinkage in IPF, and the quantitative indicator log_jac values were significantly correlated with PFTs. Key Points • The elastic registration on HRCT was helpful to quantitatively assess the deterioration of IPF. • Jacobian logarithm was significantly reduced in deteriorated patients and mean log_jac values were correlated with PFTs. • The mean log_jac values were related to the changes of pulmonary vascular volume and the number of vascular branches.

Systemic sclerosis (SSc) is a rare connective tissue disorder of unknown aetiology. Pulmonary involvement contributes substantially to its morbidity and mortality. Treatment of pulmonary disease due to SSc remains unsatisfactory. We examined the effect of sequential six-month intravenous pulse therapy with cyclophosphamide (CYC) followed by azathioprine and low-dose corticosteroids on SSc associated interstitial lung disease (SSc-ILD).In a single-centre, prospective, observational, open-labelled study; nine patients (eight females, one male) with SSc-ILD were treated with intravenous pulse CYC (600mg/m(2) body surface area) at monthly interval for six cycles with oral prednisolone 10mg daily. Subsequently, azathioprine (2-3mg/Kg) was administered while continuing with the same dose of prednisolone. Primary end-points were forced vital capacity (FVC) and high resolution computed tomography (HRCT) scan of thorax score. Secondary end-points were quality of life measured by health assessment questionnaire-disability index (HAQ-DI) and six-minute walk distance (6WMD) test.After one year of observation, the FVC showed significant improvement (p=0.003). The 6WMD also improved significantly (p=0.0028). However, change in HRCT scan scoring and HAQ-DI score was not significant.Intravenous, pulse CYC followed by azathioprine along with low-dose corticosteroids produces significant improvement in FVC and 6WMD at 12-month follow-up without significant change in radiological manifestations and health status.

Background and Objective: The optimal management of unclassifiable Interstitial lung disease (ILD) remains a challenge. The aim of this study was to describe pulmonary function trajectories for patients treated with immunomodulatory therapy and for untreated patients. Methods: Clinical information and treatment data were obtained retrospectively at two ILD centres. Pulmonary function data were analysed using (1) mixed effects linear regression models with and without clinical covariates and (2) propensity score matching using gender, age, physiology (GAP) stage, smoking and presence of ground glass opacities. Results: Sixty-five percent of the 249 patients included received corticosteroids and/or other immunomodulators. Treated patients had lower forced vital capacity (FVC) (72% vs. 83% predicted) and diffusing capacity for carbon monoxide (DLco) (44% vs. 60% predicted). In mixed effects linear regression, the adjusted change in FVC was −0.22%, [−0.34; −0.11], and −0.15% [−0.28;-0.012] for DLco. The difference in pulmonary function decline between treated and untreated patients was insignificant, −0.082% per month, [−0.28; 0.11], p = 0.10 for FVC and −0.14% per month, [−0.36; 0.079], p = 0.15, for DLco. In propensity score matched analysis, the difference in change in FVC was 0.039% per month, p = 0.12, and for DLco, 0.0085% per month, p = 0.7. Conclusion: The pulmonary function trajectories for treated and untreated patients were parallel, despite treated patients having more severe disease at baseline. The persisting differences between the groups suggest no overall effect, although improvement or stabilization may be seen in some patients. Prospective studies are needed to define subsets of patients with unclassifiable interstitial lung disease and their optimal management.

BACKGROUND: Low back pain is one of the most common musculoskeletal diseases in the modern society, causing a huge economic burden, and has become an important public health problem. Years lived with disability caused by low back pain increased rapidly as a result of population growth and ageing worldwide, with the biggest increase seen in low-income and middle-income countries. In this context, the prevention and treatment of low back pain in the elderly warrant attention and research. OBJECTIVE: The aim is to determine the correlation between vital capacity (VC) and vertebral body translation during lumbar flexion and extension in adults aged 60 to 69 years. METHODS: A total of 192 adults aged 60 to 69 years were selected by cluster sampling in Lishui City, Zhejiang Province, China. The VC of the study population was tested and the ratio of VC to body mass (BM) was calculated. The lumbar hyperextension and hyperflexion of the study population were radiographed using a Hitachi 500 mAs X-ray machine made in Japan to verify vertebral body translations in each segment. RESULTS: The differences of test values of VC (P= 0.004), VC/BM ratio (P= 0.012) and vertebral body translation in the L5-S1 segment during flexion and extension (P< 0.001) of the populations aged 60 to 64 and 65 to 69 years were all statistically significant. The vertebral body translation in the L5-S1 segment during lumbar flexion and extension in the population aged 60 to 69 years was negatively correlated with the VC (rs =-0.207 and P= 0.004) and VC/BM ratio (rs =-0.248 and P= 0.001), showing statistical significance. CONCLUSIONS: The vertebral body translation of during lumbar flexion and extension correlates with the VC in the population aged 60 to 69 years. Recognition of this correlation may help to guide further lumbar stabilization exercises.

The rapidly increasing number of COVID-19 patients has posed a massive burden on many healthcare systems worldwide. Moreover, the limited availability of diagnostic and treatment equipment makes it difficult to treat patients in the hospital. To reduce the burden and maintain the quality of care, asymptomatic patients or patients with mild symptoms are advised to self-isolate at home. However, self-isolated patients need to be continuously monitored as their health can turn into critical condition within a short time. Therefore, a portable device that can remotely monitor the condition and progression of the health of these patients is urgently needed. Here we present a portable device, called Respinos, that can monitor multiparameter vital signs including respiratory rate, heart rate, body temperature, and SpO2. It can also operate as a spirometer that measures forced vital capacity (FVC), forced expiratory volume (FEV), FEV in the first second (FEV1), and peak expiratory flow Rate (PEFR) parameters which are useful for detecting pulmonary diseases. The spirometer is designed in the form of a tube that can be ergonomically inflated by the patient, and is equipped with an accurate and disposable turbine based air flow sensor to evaluate the patient's respiratory condition. Respinos uses rechargeable batteries and wirelessly connects to a mobile application whereby the patient's condition can be monitored in real-time and consulted with doctors via chat. Extensive comparison against medical-grade reference devices showed good performance of Respinos. Overall results demonstrate the potential of Respinos for remote patient monitoring during and post pandemic.

Xingyao Tang,1– 4 Jieping Lei,2,3,5,6 Wei Li,1– 3,5 Yaodie Peng,1,7 Chen Wang,1– 3,5 Ke Huang,1– 3,5,&ast; Ting Yang1– 3,5,&ast; 1Department of Pulmonary and Critical Care Medicine, China-Japan Friendship Hospital, Beijing, 100029, People’s Republic of China; 2National Center for Respiratory Medicine, Beijing, 100029, People’s Republic of China; 3National Clinical Research Center for Respiratory Diseases, Beijing, 100029, People’s Republic of China; 4Capital Medical University, Beijing, 10069, People’s Republic of China; 5Institute of Respiratory Medicine, Chinese Academy of Medical Sciences, Beijing, 100029, People’s Republic of China; 6Department of Clinical Research and Data Management, Center of Respiratory Medicine, China-Japan Friendship Hospital, Beijing, 100029, People’s Republic of China; 7Peking University Health Science Center, Beijing, 10029, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ke Huang; Ting Yang, China-Japan Friendship Hospital, Beijing, 100029, People’s Republic of China, Tel +010-8420 6275, Email huangke_zryy@163.com; dryangting@qq.comPurpose: To analyze the relationship between body mass index (BMI) and lung function, which may help optimize the screening and management process for chronic obstructive pulmonary disease (COPD) in the early stages.Patients and Methods: In this cross-sectional study using data from the Enjoying Breathing Program in China, participants were divided into two groups according to COPD Screening Questionnaire (COPD-SQ) scores (at risk and not at risk of COPD) and three groups based on lung function (normal lung function, preserved ratio impaired spirometry [PRISm], and obstructive lung function).Results: A total of 32,033 subjects were enrolled in the current analysis. First, in people at risk of COPD, overweight and obese participants had better forced expiratory volume in one second (FEV1; overweight: 0.33 liters (l), 95% confidence interval [CI]: 0.27 to 0.38; obesity: 0.31 L, 95% CI: 0.22 to 0.39) values than the normal BMI group. Second, among people with PRISm, underweight participants had a lower FEV1 (− 0.56 L, 95% CI: − 0.86 to − 0.26) and forced vital capacity (FVC; − 0.33 L, 95% CI: − 0.55 to − 0.11) than participants with a normal weight, and obese participants had a higher FEV1 (0.22 L, 95% CI: 0.02 to 0.42) and FVC (0.16 L, 95% CI: 0.02 to 0.30) than participants with a normal weight. Taking normal BMI as the reference group, lower FEV1 (− 0.80 L, 95% CI: − 0.97 to − 0.63) and FVC (− 0.53 L, 95% CI: − 0.64 to − 0.42) were found in underweight participants with obstructive spirometry, and better FEV1 (obesity: 0.26 L, 95% CI: 0.12 to 0.40) was found in obese participants with obstructive spirometry.Conclusion: Being underweight and severely obese are associated with reduced lung function. Slight obesity was shown to be a protective factor for lung function in people at risk of COPD and those with PRISm.Keywords: body mass index, lung function, preserved ratio impaired spirometry, chronic obstructive pulmonary disease

Objective: The study aimed to investigate the value of pulmonary function test (PFT) in evaluating and predicting pulmonary arterial hypertension (PAH) in patients with connective tissue disease (CTD). Methods: This was a prospective observational study recruiting patients diagnosed with CTD-PAH. Patients with interstitial lung disease and pulmonary hypertension induced by other causes were not eligible for enrollment. All patients were assessed for PAH every 1–3 months. A patient was considered to have clinical improvement if the grade of risk stratification declined or at least two parameters improved during follow-up, otherwise no improvement. Results: A total of 31 patients with CTD-PAH were recruited in this study. Nearly 70% of patients had declined forced vital capacity (FVC), 60% had declined total lung capacity and maximum expiratory flow at 50% of vital capacity, and 95% had normal or mild decline in forced expiratory volume in 1 second (FEV1)/FVC. A decline in diffusing capacity of the lung for carbon monoxide (DLCO) was present in 96% of patients, and 60% were moderate to severe. Furthermore, 50% of patients had an FVC/DLCO ratio of less than 1.4. Univariate analysis showed that FEV1/FVC, DLCO, and FVC/DLCO were associated with disease prognosis. After adjusting for age as a confounding factor, multivariate logistic regression analysis revealed that DLCO was an independent predictive factor for the prognosis of CTD-PAH. Conclusion: The pulmonary function of patients with CTD-PAH is abnormal in parameters such as lung volume, small airway, and gas exchange. PFT can reveal complex pathophysiological changes in the lungs of CTD-PAH patients and predict prognosis.

Background: We investigated the relationship between respiratory function measured by spirometry analysis and anthropometric variables (skeletal and fat mass) and nutritional status in the institutionalized elderly, particularly at high-risk for adverse outcomes after respiratory infections and malnutrition. Design: This is a multicenter cross-sectional study with a quantitative approach conducted among older people institutionalized living in nursing homes. Methods: Respiratory function was assessed by measuring the forced vital capacity, forced expiratory volume in the first second, the ratio between FEV1 and FVC (FEV1/FVC), and peak expiratory flow in percentage by means of spirometric analysis (values of the forced expiratory volume measured during the first second of the forced breath (FEV1) and forced vital capacity (FVC)). Nutritional assessment and anthropometry analyses were performed to evaluate under or over nutrition/weight. Results: There was a significant (p70% with FEV1 and FVC150 mg/dl) (OR=5.59). Conclusion: The relationship between a restrictive pattern of respiratory function and fat mass deserves future investigation to manage these parameters as a possible modifiable factor of altered respiratory function in overweight institutionalized older individuals.

Guoyan Tang,1,&ast; Fengyan Wang,1,&ast; Zhenyu Liang,1,&ast; Cuixia Liang,2,&ast; Jinling Wang,3,&ast; Yuqiong Yang,1 Wanyi Tang,1,4 Weijuan Shi,1 Guoqiang Tang,3 Kai Yang,5 Zihui Wang,1 Qiasheng Li,1 Hualin Li,1 Jiaxuan Xu,1 Deyan Chen,2 Rongchang Chen5 1State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, People’s Republic of China; 2Neusoft Medical Systems Co., Ltd, Shenyang, People’s Republic of China; 3Qingyuan Chronic Disease Prevention Hospital, Qingyuan Occupational Disease Prevention Hospital, Qingyuan, People’s Republic of China; 4Qingyuan People’s Hospital, the Sixth Affiliated Hospital of Guangzhou Medical University, Guangzhou, People’s Republic of China; 5Department of Respiratory and Critical Care Medicine, First Affiliated Hospital of Southern University of Science and Technology, Second Clinical Medical College of Jinan University, Shenzhen People’s Hospital, Shenzhen Institute of Respiratory Diseases, Shenzhen, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Rongchang Chen, Department of Respiratory and Critical Care Medicine, First Affiliated Hospital of Southern University of Science and Technology, Second Clinical Medical College of Jinan University, Shenzhen People’s Hospital, Shenzhen Institute of Respiratory Diseases, Shenzhen, People’s Republic of China, Email chenrc@vip.163.com Zhenyu Liang, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, People’s Republic of China, Email 490458234@qq.comBackground: Pulmonary vascular alteration is an important feature of chronic obstructive pulmonary disease (COPD), which is characterized by distal pulmonary vascular pruning in angiography. We aimed to further investigate the clinical relevance of pulmonary vasculature in COPD patients using non-contrast computed tomography (CT).Methods: Seventy-one control subjects and 216 COPD patients completed the questionnaires, spirometry, and computed tomography (CT) scans within 1 month and were included in the study. Small pulmonary vessels represented by percentage of cross-sectional area of pulmonary vessels smaller than 5 mm2 or 5– 10 mm2 to the total lung fields (%CSA< 5 or %CSA5– 10, respectively) were measured using ImageJ software. Spearman correlation was used to investigate the relationship between %CSA< 5 and airflow limitation. A receiver operating characteristic (ROC) curve was built to evaluate the value of %CSA< 5 in discriminating COPD patients from healthy control subjects. Segmented regression was used to analyze the relationship between %CSA< 5 and %LAA-950 (percentage of low-attenuation areas less than − 950 HU).Results: We found a significant correlation between %CSA< 5 and forced expiratory volume in one second (FEV1) percentage of predicted value (%pred) (r = 0.564, P < 0.001). The area under the ROC curve for the value of %CSA< 5 in distinguishing COPD was 0.816, with a cut-off value of 0.537 (Youden index J, 0.501; sensitivity, 78.24%; specificity, 71.83%). Since the relationship between %CSA< 5 and %LAA-950 was not constant, performance of segmented regression was better than ordinary linear regression (adjusted R2, 0.474 vs 0.332, P < 0.001 and P < 0.001, respectively). As %CSA< 5 decreased, %LAA-950 slightly increased until an inflection point (%CSA< 5 = 0.524) was reached, after which the %LAA-950 increased apparently with a decrease in %CSA< 5.Conclusion: %CSA< 5 was significantly correlated with both airflow limitation and emphysema, and we identified an inflection point for the relationship between %CSA< 5 and %LAA-950.Keywords: computed tomography, pulmonary vascular pruning, airflow limitation, emphysema, chronic obstructive pulmonary disease

Pulmonary rehabilitation is a cornerstone of management for patients after lung transplantation (LT), but the benefits of inspiratory muscle training (IMT) after LT in children are unclear. Therefore, we examined whether IMT can improve respiratory function and dyspnoea in a paediatric patient after LT.The patient was a 13-year-old boy who underwent double LT. However, mild physical activity such as walking triggered dyspnoea for the patient. The patient underwent IMT with the intensity of approximately 30% of his maximal inspiratory pressure (MIP) for 2 months.The patient’s MIP was increased by approximately 60% after 2 months, and his forced vital capacity as a percent of the predicted normal value increased from 74.6% to 83.4%, with improvement of dyspnoea.IMT may help improve dyspnoea after LT in children with respiratory muscle weakness and a decline in respiratory function.

Objective. To observe the effects of core stabilization training on the Cobb angle, respiratory muscle strength (maximum inspiratory pressure, MIP; maximal expiratory pressure, MEP), and pulmonary function (forced vital capacity, FVC; forced expiratory volume, FEV1.0; FEV1.0/FVC%) in adolescent patients with idiopathic scoliosis (AIS) and offer practical-based evidence for the rehabilitation treatment for AIS patients. Methods. 36 AIS patients were assigned to the core stability training (CST) group (n = 18) and control group (n = 18); the CST group participated in three sessions of core stabilization exercise per week for 12 weeks and the control group did not perform regular physical training during 12 weeks of study. Then, the Cobb angle, respiratory muscle strength (MIP and MEP), and pulmonary function (FVC, FEV1.0, and FEV1.0/FVC%) were measured before and after core stabilization training. Results. After 12 weeks of core stabilization training, compared with the pretest, the Cobb angle showed a significant decrease, FVC, FEV1, MIP, and MEP a significant increase ( P < 0.01 respectively), and there was no statistical difference in FEV1/FVC in the CST group; there was no significant difference ( P > 0.05 respectively) before and after an experiment in the control group except MEP decreased significantly ( P < 0.01 , P < 0.05 ). After 12 weeks of core stabilization training, compared with the control group, the Cobb angle significantly decreased ( P < 0.01 ), FVC, FEV1, MIP, and MEP significantly increased ( P < 0.05 respectively) in the CST group, but there was no significant difference ( P > 0.05 , respectively) in FEV1/FVC between the control group and CST group. Conclusions. Core stabilization exercise can be considered to have a positive effect on the normal physiological curvature of the spine in AIS patients, as it decreases the Cobb angle and strengthens respiratory muscle strength and pulmonary function.

Prediction of disease course in patients with progressive pulmonary fibrosis remains challenging. The purpose of this study was to assess the prognostic value of lung fibrosis extent quantified at computed tomography (CT) using data-driven texture analysis (DTA) in a large cohort of well-characterized patients with idiopathic pulmonary fibrosis (IPF) enrolled in a national registry.This retrospective analysis included participants in the Australian IPF Registry with available CT between 2007 and 2016. CT scans were analysed using the DTA method to quantify the extent of lung fibrosis. Demographics, longitudinal pulmonary function and quantitative CT metrics were compared using descriptive statistics. Linear mixed models, and Cox analyses adjusted for age, gender, BMI, smoking history and treatment with anti-fibrotics were performed to assess the relationships between baseline DTA, pulmonary function metrics and outcomes.CT scans of 393 participants were analysed, 221 of which had available pulmonary function testing obtained within 90 days of CT. Linear mixed-effect modelling showed that baseline DTA score was significantly associated with annual rate of decline in forced vital capacity and diffusing capacity of carbon monoxide. In multivariable Cox proportional hazard models, greater extent of lung fibrosis was associated with poorer transplant-free survival (hazard ratio [HR] 1.20, p 0.0001) and progression-free survival (HR 1.14, p 0.0001).In a multi-centre observational registry of patients with IPF, the extent of fibrotic abnormality on baseline CT quantified using DTA is associated with outcomes independent of pulmonary function.

Purpose In 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. Methods In 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. Results Lower 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 2O and 1.31 ± 0.39 ml/cmH2O, respectively (p Conclusion In 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.

Purpose This study aimed to investigate the association between the results of pulmonary function tests (PFTs) in patients with chronic obstructive pulmonary disease (COPD) and the size of their diaphragmatic crus (DC) using inspiratory and expiratory CT. Materials and methods Thirty-three patients who underwent inspiratory and expiratory CT and PFTs between July and December 2019 were studied retrospectively. The short axis, long axis, and cross-sectional area (CSA) of the bilateral DC were measured, and the percentage change of the DC after expiration (% change of DC) in the size was calculated. The correlation between the results of the PFTs (forced expiratory volume in 1 s [FEV1], FEV1/forced vital capacity [FVC], and percent predicted FEV1 [%FEV1]) and the size and % change of DC was statistically analyzed. Results Significant correlations were observed between the short axis of the right and left DC at expiration and PFTs (FEV1, r = –0.35, –0.48, p = 0.04, .007; FEV1/FVC, r = –0.52, –0.65, p = 0.002, 1, r = –0.56, –0.60, p 1/FVC, r = –0.42, p = 0.01; %FEV1, r = –0.41, p = 0.017; respectively), and between the % change of the short axis of the left DC and the CSA of the left DC and PFTs (FEV1, r = 0.64, 0.56, p 1, r = 0.52, 0.51, p = 0.004, 0.004; respectively). The smaller the short axis of the DC and CSA at expiration and the larger the % change in DC of the CSA, the lower the airflow limitation. Conclusion There were significant correlations between airflow limitation and the short axis of the bilateral DC at expiration, and the % change in the DC of the CSA. Certain CT measurements of the DC may reflect airflow limitation in patients with COPD.

A decline in lung function is the basis of the definition of progressive fibrosing interstitial lung disease. This study aimed to evaluate the epidemiology and clinical relevance of lung function decline in sarcoidosis.This retrospective observational study was conducted at a general sarcoidosis clinic. Lung function decline was defined as a relative 24-month decline in the percentage of predicted forced vital capacity (%FVC) of ≥10% or the percentage of predicted diffusion capacity for carbon monoxide (%DLco) of ≥15%. The frequency of lung function decline and its associations with the subsequent 24-month change in lung function and survival time were analyzed.Of the 201 patients, 14 (7.0%) exhibited a 24-month decline in %FVC of ≥10% and 28 (16.6%) exhibited a 24-month decline in %DLco of ≥15%. A 24-month decline in lung function was not associated with a subsequent 24-month lung function decline. Eleven patients died during the median observational time of 148.3 months; 4 of the 11 deaths were associated with sarcoidosis. A 24-month decline in lung function was associated with worse survival even after the adjustment for composite physiological index (CPI) and pulmonary hypertension (PH): 24-month decline in %FVC ≥10%, hazard ratio (HR) adjusted for CPI = 21.8, HR adjusted for PH = 19.3 and 24-month decline in %DLco ≥15%, HR adjusted for PH = 6.74.A 24-month decline in lung function can be a risk factor for mortality in sarcoidosis irrespective of CPI and PH.

The antifibrotic agent nintedanib has been reported to effectively prevent the decline in forced vital capacity (FVC) in a broad range of interstitial lung diseases. However, the efficacy of nintedanib against idiopathic pleuroparenchymal fibroelastosis (iPPFE) remains unclear.We retrospectively examined patients with idiopathic PPFE or idiopathic pulmonary fibrosis (IPF) who received nintedanib for more than 6 months. We evaluated annual changes in %FVC, radiological PPFE lesions, and body weight before and during nintedanib treatment. To investigate radiological PPFE lesions, we examined the fibrosis score, which was defined as the mean percentage of the high attenuation area in the whole lung parenchyma using three axial computed tomography images.Overall, 15 patients with iPPFE and 27 patients with IPF were included in the present study. In patients with IPF, the annual rate of decline in %FVC was significantly lower during nintedanib treatment than that before treatment (-2.01%/year [-7.64 to 3.21] versus -7.64%/year [-10.8 to -4.44], p = 0.031). Meanwhile, in patients with iPPFE, the annual rate of decline in %FVC during nintedanib treatment was higher than that before treatment (-18.0%/year [-21.6 to -12.7] versus -9.40%/year [-12.3 to -8.23], p = 0.109). In addition, nintedanib treatment failed to inhibit the annual rate of increase in fibrosis score in patients with iPPFE (6.53/year [1.18-15.3] during treatment versus 2.70/year [0.27-12.2] before treatment, p = 0.175).Nintedanib efficacy may be limited in patients with iPPFE.

ALS is a heterogeneous disease that may be complicated or in part driven by inflammation. NP001, a regulator of macrophage activation, was associated with slowing disease progression in those with higher levels of the plasma inflammatory marker C-reactive protein (CRP) in phase 2A studies in ALS. Here, we evaluate the effects of NP001 in a phase 2B trial, and perform a post hoc analysis with combined data from the preceding phase 2A trial.The phase 2B trial enrolled 138 participants within 3 y of symptom onset and with plasma hs-CRP values1.13 mg/L. They were randomized 1:1 to receive either placebo or NP001 for 6 mo. Change from baseline ALSFRS-R scores was the primary efficacy endpoint. Secondary endpoints included vital capacity (VC) change from baseline and percentage of participants showing no decline of ALSFRS-R score over 6 mo (non-progressor).The phase 2B study did not show significant differences between placebo and active treatment with respect to change in ALSFRS-R scores, or VC. The drug was safe and well tolerated. A post hoc analysis identified a 40- to 65-y-old subset in which NP001-treated patients demonstrated slower declines in ALSFRS-R score by 36% and VC loss by 51% compared with placebo. A greater number of non-progressors were NP001-treated compared with placebo (p = .004).Although the phase 2B trial failed to meet its primary endpoints, post hoc analyses identified a subgroup whose decline in ALSFRS-R and VC scores were significantly slower than placebo. Further studies will be required to validate these findings.

Human epidemiological studies have shown inconclusive results over the effects of diisocyanates on respiratory health problems. A meta-analysis combined evidence on the association between occupational asthma (OA), respiratory function, and toluene diisocyanate (TDI) inhalation exposure. Sixty-one articles on occupational toluene diisocyanate exposure were identified via two databases. Fourteen studies were included in the meta-analysis. The Newcastle-Ottawa Scale (NOS) was used to assess the quality of the studies. Odds ratios (ORasthma) for the association between TDI exposure compared to non-exposure and OA were calculated. The difference in mean differences (MD) of forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC), and the annual mean change differences—in milliliters per year (mL/yr)—in FEV1 and FVC pulmonary function between TDI exposed and non-exposed, were calculated. When applicable, a random effects meta-analysis was performed. The overall summary ORasthma for TDI exposed versus non-exposed was 1.18 (95% CI = 0.78–1.79). The summary of the predicted mean percentage difference (MD%predicted) between exposed versus non-exposed was 2.96% for FEV1 and 3.75% for FVC. A very small decrease of 5 mL/yr for FEV1 and 10 mL/yr for FVC, respectively, was observed between the exposed and the non-exposed groups. There was moderate to low heterogeneity between study results, and most studies were evaluated as high-quality. This meta-analysis found no statistically significant adverse association between TDI occupational exposure and OA. No meaningful differences in lung function were detected between exposed and unexposed groups.

To analyze the efficacy and safety of nintedanib in patients with fibrosing autoimmune disease-related interstitial lung diseases (ILDs) with a progressive phenotype.The INBUILD trial enrolled patients with a fibrosing ILD other than idiopathic pulmonary fibrosis, with diffuse fibrosing lung disease of10% extent on high-resolution computed tomography, forced vital capacity percent predicted (FVC%) ≥45%, and diffusing capacity of the lungs for carbon monoxide percent predicted ≥30% to80%. Patients fulfilled protocol-defined criteria for progression of ILD within the 24 months before screening, despite management deemed appropriate in clinical practice. Subjects were randomized to receive nintedanib or placebo. We assessed the rate of decline in FVC (ml/year) and adverse events (AEs) over 52 weeks in the subgroup with autoimmune disease-related ILDs.Among 170 patients with autoimmune disease-related ILDs, the rate of decline in FVC over 52 weeks was -75.9 ml/year with nintedanib versus -178.6 ml/year with placebo (difference 102.7 ml/year [95% confidence interval 23.2, 182.2]; nominal P = 0.012). No heterogeneity was detected in the effect of nintedanib versus placebo across subgroups based on ILD diagnosis (P = 0.91). The most frequent AE was diarrhea, reported in 63.4% and 27.3% of subjects in the nintedanib and placebo groups, respectively. AEs led to permanent discontinuation of trial drug in 17.1% and 10.2% of subjects in the nintedanib and placebo groups, respectively.In the INBUILD trial, nintedanib slowed the rate of decline in FVC in patients with progressive fibrosing autoimmune disease-related ILDs, with AEs that were manageable for most patients.

Nontuberculous mycobacterial (NTM) infections are difficult to diagnose and treat. Biomarkers to identify patients with active infection or at risk of disease progression would have clinical utility. Sputum is the most frequently used matrix for the diagnosis of NTM lung disease.Can sputum proteomics be used to identify NTM-associated inflammatory profiles in sputum?Patients with NTM lung disease and a matched cohort of patients with COPD, bronchiectasis (BE), and cystic fibrosis (CF) without NTM lung disease were enrolled from two hospitals in the United Kingdom. Liquid chromatography-tandem mass spectrometry was used to identify proteomic biomarkers associated with underlying diagnosis (COPD, BE, and CF), the presence of NTM lung disease defined according to American Thoracic Society/Infectious Diseases Society of America criteria, and severity of NTM. A subset of patients receiving guideline-concordant NTM treatment were studied to identify protein changes associated with treatment response.This study analyzed 95 sputum samples from 55 subjects (BE, n = 21; COPD, n = 19; CF, n = 15). Underlying disease and infection with Pseudomonas aeruginosa were the strongest drivers of sputum protein profiles. Comparing protein abundance in COPD, BE, and CF found that 12 proteins were upregulated in CF compared with COPD, including MPO, AZU1, CTSG, CAT, and RNASE3, with 21 proteins downregulated, including SCGB1A1, IGFBP2, SFTPB, GC, and CFD. Across CF, BE, and COPD, NTM infection (n = 15) was not associated with statistically significant differences in sputum protein profiles compared with those without NTM. Two proteins associated with iron chelation were significantly downregulated in severe NTM disease. NTM treatment was associated with heterogeneous changes in the sputum protein profile. Patients with NTM and a decrease in immune response proteins had a subjective symptomatic improvement.Sputum proteomics identified candidate biomarkers of NTM severity and treatment response. However, underlying lung disease and typical bacterial pathogens such as P aeruginosa are also key determinants of the sputum proteomic profile.

The purpose of the study was to investigate pulmonary functions of patients with chronic neck pain and compare them with those of asymptomatic controls.This case-control study was conducted with 25 patients with chronic neck pain (age, 26.84 ± 7.89 years) and 27 age-matched asymptomatic controls (age, 25.96 ± 7.13 years). Pulmonary function tests were performed using spirometry (Quark PFT, COSMED, Rome, Italy). Forced vital capacity (FVC), forced expiratory volume in the first second (FEVThe chronic neck pain group had lower FEVThese results demonstrated that dynamic lung volumes were lower in patients with chronic neck pain compared with asymptomatic controls.

Background With an increase in published reports on respiratory rehabilitation (RR) in severe acute respiratory syndrome (SARS), there is a need for a meta-analysis and systematic review to measure the effects of the RR in SARS. Objective Objective of the review was to evaluate the efficacy and safety of RR in patients recovering from SARS. Methods PubMed/ MEDLINE, CENTRAL, EMBASE, and Clinical Trial Registries were systematically searched (between January 1, 2003, to July 31, 2021) to identify all patients who received RR, at least for six days, following SARS. The primary outcome was exercise capacity [6-meter walking distance (6-MWD)], and secondary outcomes were change in pulmonary function test (PFT) parameters, activities in daily livings (ADLs), and quality of life (QoL). Meta-analysis was performed by using RevMan 5.4. Results Twenty-one observational studies, including eight comparative studies, were included. Eight comparative studies participated in quantitative meta-analysis. The intervention group, who received RR, improved significantly in exercise capacity (6-MWD) [mean difference (MD):45.79, (95% CI:31.66–59.92)] and PFT parameters, especially in forced vital capacity (FVC%) [MD:4.38, (95% CI:0.15–8.60)], and diffusion lung capacity for carbon monoxide (DLCO%) [MD:11.78, (95% CI:5.10–18.46)]. The intervention group failed to demonstrate significant improvement in ADLs and QoL outcomes. No significant adverse events were reported during the intervention. Conclusion Respiratory rehabilitation can improve exercise capacity and PFT parameters in patients recovering from SARS infection. The RR does not cause serious adverse events. Clinical trials to determine the best RR program (in terms of initiation, duration, and components) in SARS and its treatment efficacy, both in the short and long- term are needed.

© 2022 European Academy of Neurology., Background and purpose Progression rate is quite variable in amyotrophic lateral sclerosis (ALS); thus, tools for profiling disease progression are essential for timely interventions. The objective was to apply dynamic Bayesian networks (DBNs) to establish the influence of clinical and demographic variables on disease progression rate. Methods In all, 664 ALS patients from our database were included stratified into slow (SP), average (AP) and fast (FP) progressors, according to the Amyotrophic Lateral Sclerosis Functional Rating Scale Revised (ALSFRS-R) rate of decay. The sdtDBN framework was used, a machine learning model which learnt optimal DBNs with both static (gender, age at onset, onset region, body mass index, disease duration at entry, familial history, revised El Escorial criteria and C9orf72) and dynamic (ALSFRS-R scores and sub-scores, forced vital capacity, maximum inspiratory pressure, maximum expiratory pressure and phrenic amplitude) variables. Results Disease duration and body mass index at diagnosis are the foremost influences amongst static variables. Disease duration is the variable that better discriminates the three groups. Maximum expiratory pressure is the respiratory test with prevalent influence on all groups. ALSFRS score has a higher influence on FP, but lower on AP and SP. The bulbar sub-score has considerable influence on FP but limited on SP. Limb function has a more decisive influence on AP and SP. The respiratory sub-score has little influence in all groups. ALSFRS-R questions 1 (speech) and 9 (climbing stairs) are the most influential in FP and SP, respectively. Conclusions The sdtDBN analysis identified five variables, easily obtained during clinical evaluation, which are the most influential for each progression group. This insightful information may help to improve prognosis and care.

Objective To evaluate the efficacy and safety of pulmonary rehabilitation for exercise tolerance and quality of life improvement in idiopathic pulmonary fibrosis. Methods We searched PubMed, Cochrane Library, Embase, Web of Science, Chinese Biomedical Literature Database, China National Knowledge Infrastructure, Wanfang Database, and Chongqing VIP for randomized controlled trials that compared pulmonary rehabilitation with usual care for idiopathic pulmonary fibrosis. The risk of bias and certainty of evidence were assessed using Cochrane Collaboration’s Risk of Bias tool and the Grading of Recommendations, Assessment, Development and Evaluation criteria. Results Eleven trials in total with 549 participants. Compared with usual care, pulmonary rehabilitation significantly increased 6-minute walking distance (mean difference: 35.2m, 95% confidence intervals: 25.4m–44.9m; ten trials; 447 participants; moderate), decreased the St George's Respiratory Questionnaire total scores (mean difference: −9.11, 95% confidence intervals: −10.78 to −7.43; six trials; 303 participants; moderate), and reduced the modified Medical Research Council scores were lower (mean difference: −0.76, 95% confidence intervals: −1.25 to −0.27; three trials; 196 participants; low). Improvements were noted in forced vital capacity percent-predicted (mean difference: 4.88, 95% confidence intervals: 2.67 to 7.10; four trials; 214 participants; moderate) and diffusing capacity for carbon monoxide (mean difference: 4.71, 95% confidence intervals: 0.96 to 8.46; six trials; 358 participants; low). Conclusions Pulmonary rehabilitation may significantly improve exercise tolerance and quality of life in idiopathic pulmonary fibrosis patients, but the quality of evidence was low to moderate. Large sample, multicenter, randomized controlled trials are needed to verify the efficacy and safety of pulmonary rehabilitation.

It is unclear whether the frequency and mechanisms of expiratory flow limitation (EFL) during exercise differ between males and females.This study aimed to determine which factors predispose individuals to EFL during exercise and whether these factors differ based on sex. We hypothesized that i) EFL frequency would be similar in males and females and ii) in females, EFL would be associated with indices of low ventilatory capacity, whereas in males, EFL would be associated with indices of high ventilatory demand.Data from n = 126 healthy adults (20-45 y, n = 60 males, n = 66 females) with a wide range of cardiorespiratory fitness (81%-182% predicted maximal oxygen uptake) were included in the study. Participants performed spirometry and an incremental cycle exercise test to exhaustion. Standard cardiorespiratory variables were assessed throughout exercise. The tidal flow-volume overlap method was used to assess EFL based on a minimum threshold of 5% overlap between the tidal and the maximum expiratory flow-volume curves. Predictors of EFL during exercise were determined via multiple logistical regression using anthropometric, pulmonary function, and peak exercise data.During exercise, EFL occurred in 49% of participants and was similar between the sexes (females = 45%, males = 53%; P = 0.48). In males, low forced expired flow between 25% and 75% of forced vital capacity and high slope ratio as well as low end-expiratory lung volume, high breathing frequency, and high relative tidal volume at peak exercise were associated with EFL ( P0.001; Nagelkerke R2 = 0.73). In females, high slope ratio, high breathing frequency, and tidal volume at peak exercise were associated with EFL ( P0.001; Nagelkerke R2 = 0.61).Despite sex differences in respiratory system morphology, the frequency and the predictors of EFL during exercise do not substantially differ between the sexes.

To examine changes in lung function over time in extremely prematurely born adolescents.Changes in lung function during adolescence would vary by ventilation mode immediately after birth.Longitudinal follow-up study.Participants from the United Kingdom Oscillation Study who were randomized at birth to high-frequency oscillation (HFO) or conventional ventilation (CV) were assessed at 11-14 years (n = 319) and at 16-19 years (n = 159).Forced expiratory flow (FEF), forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), and lung volumes including functional residual capacity (FRC) were reported as z-scores. The diffusion capacity of the lungs for carbon monoxide (DLCO) was measured. Lung function trajectories were compared by mode of ventilation using mixed models. Changes in z-scores were scaled to 5-year average follow-up.There were significant changes in the mean FEF75, FEF50, FEF25, FEV1, FVC, and DLCO z-scores within the CV and HFO cohorts, but no significant differences in the changes between the two groups. The mean FRC z-score increased in both groups, with an average change of greater than one z-score. The mean FEV1/FVC z-score increased significantly in the CV group, but not in the HFO group (difference in slopes: p = 0.02). Across the population, deterioration in lung function was associated with male sex, white ethnicity, lower gestational age at birth, postnatal corticosteroids, oxygen dependency at 36 weeks postmenstrual age, and lower birth weight, but not ventilation mode.There was little evidence that the mode of ventilation affected changes in lung function over time.

Background Small airways are known to be affected early in the course of chronic obstructive pulmonary disease (COPD); however, traditional spirometric indices may not accurately identify small airways disease. Research Question Can FEV3/FEV6 identify early airflow abnormalities and predict future clinically important respiratory-related outcomes, including development of COPD? Study Design and Methods We included eight hundred thirty-two current and former smokers with post-bronchodilator FEV1/FVC ≥0.7 from the SPIROMICS cohort. Participants were classified as having a reduced pre-bronchodilator FEV3/FEV6 based on lower limit of normal (LLN) values. Repeatability analysis was performed for FEV3 and FEV6. Regression modeling was used to evaluate the relationship between baseline FEV3/FEV6 and outcome measures including functional small airways disease on thoracic imaging and respiratory exacerbations. Interval censored analysis was used to assess progression to COPD. Results FEV3/FEV6 Interpretation FEV3/FEV6 is a routinely available and repeatable spirometric index which can be useful in the evaluation of early airflow obstruction in current and former smokers without COPD. A reduced FEV3/FEV6 can identify those at risk for future development of COPD and respiratory exacerbations.

Background Although male sex is associated with poor prognosis in Systemic Sclerosis (SSc), it is unclear whether this association is independent of confounding factors such as occupational exposure to toxicants. Research Question What is the respective impact of sex and occupational exposure on SSc patients’ characteristics with a focus on lung function decline? Study Design and Methods Patients with SSc (n=210, 55 males) underwent standardized quantitative assessment of occupational exposure through a cumulative exposure score (CES) in a multicenter recruitment retrospective cohort. Association of the CES with patients’ characteristics was assessed. Mixed linear, logistic and Cox regression models were used to identify predictors of time variation of forced vital capacity (FVC) and the hemoglobin-corrected transfer coefficient for carbon monoxide in the lung (DLCOc). Results Male sex was strongly associated with occupational exposure (OR=10.3, p Interpretation Occupational exposure to toxicants appears to independently predict decline of FVC in SSc patients, regardless of sex. Assessment of occupational exposure may be useful for SSc prognostication.

Background Residual structural changes in the lung along with pulmonary impairment remain in a large number of patients of tuberculosis after microbiological cure. The aim of this study was to determine whether 12 weeks of a structured pulmonary rehabilitation program (PRP) administered along with antitubercular treatment improved the baseline measurement of pulmonary function, exercise capacity, and health-related quality of life (HRQOL). Methods A pilot study with single blind randomized control design was carried out in a tertiary care chest center. Spirometry, exercise capacity by 6-minute walk distance (6MWD), and HRQOL using St George respiratory questionnaire (SGRQ) score were evaluated in 62 patients, divided into 2 groups: intervention group (IG) (n = 31) and control group (CG) (n = 31) patients at baseline and at end of 12 weeks. IG completed 12 weeks of PRP. Results Significant difference in forced expiratory volume in 1st second (FEV1) (2.94 L at baseline vs 3.18 L at end of 12 weeks of PRP, diff 0.239 L, p-0.001), forced vital capacity (FVC) (3.43 L vs 3.75L, p −0.00), 6MWD (440.6 m vs 574.6 m, p = 0.00), and SGRQ score of at baseline (24.5 m vs 11.1m, p = 0.00) was seen in the IG. At end of 12 weeks, there was statistically significant difference in FEV1(L) (p = 0.01, 95% CI −0.317 to −0.046), FVC(L) (p = 0.00, 95% CI −0.359 to −0.139),6MWD(m) (p = 0.00; 95% CI −101.6 to −49.57) between CG and IG. There was no statistically significant difference in SGRQ scores between the 2 groups (p = 0.231). Conclusion PRP administered along with treatment is beneficial in reducing residual pulmonary impairment.

Bronchodilation testing is an important component of spirometry testing, and omitting this procedure has potential clinical implications toward diagnosing respiratory diseases. We aimed to estimate the impact of bronchodilator testing in accurately diagnosing COPD and differentiating COPD from asthma-COPD overlap (ACO).The National Health and Nutrition Examination Survey data were analyzed from 2007-2012. Airflow limitation was defined by FEVWe identified 11,763 subjects ≥ 40 y of age eligible for spirometry; 625 of them had a pre-bronchodilator FEVSpirometry with bronchodilation is an important element in the accurate diagnosis of ACO and COPD. Spirometry performed without bronchodilator testing may lead to an estimated misclassification of ACO by 7.6% to 19.8% and overdiagnosis of COPD by 39%.

To examine objective daytime predictors of nocturnal hypercapnic hypoventilation (NHH) and identify a forced vital capacity (FVC) z-score cut off that predicts NHH using the 2012 Global Lung Function Initiative (GLI) reference equations in pediatric neuromuscular patients.Single-centre retrospective medical record review.Tertiary pediatric hospital in Australia.Children (18 years old) with a neuromuscular disorder (NMD) who had a diagnostic sleep study over a 5-year period.Fifty children were included, median age 11.9 years (interquartile range [IQR]: 4.5-14.3). The majority of children had a diagnosis of Duchenne Muscular Dystrophy (32%). NHH was diagnosed in 18 children (36%). Multivariate logistic regression analysis performed for the entire cohort confirmed a statistically significant association between NHH and scoliosis (odds ratio [OR]: 3.3, p = 0.03), but not age (OR: 1.01, p = 0.26), body mass index z-score (OR: 0.86, p = 0.26) or use of a wheelchair for mobility (OR: 1.25, p = 0.72). For the subset of 29 children who had spirometry testing (median age 12.9 years [IQR: 10.2-14.3]), FVC z-score was the only statistically significant predictor of NHH (OR: 0.45, p = 0.02). NHH was predicted by an FVC z-score-3.24 (sensitivity 78%, specificity 73%), or FVC60% predicted (sensitivity 78%, specificity 73%). There was a strong positive correlation between FVC and forced expiratory volume in 1 s z-scores (rChildren with a NMD and scoliosis or a lower FVC z-score have increased odds of having NHH.

Objective. Asthma is defined as a heterogeneous disease that is usually characterized by chronic airway inflammation. Long noncoding RNAs play important roles in various biological processes including inflammation. To know more about the relationships between lncRNAs and asthma, we sought to the role of LINC00847 in peripheral blood mononuclear cells (PBMCs) of children with asthma exacerbation or asthma remission. Methods. Microarray analysis was performed on GSE143192 and GSE165934 datasets to screen differentially expressed lncRNAs (DElncRNAs) in human PBMCs between asthma patients and normal controls. LINC00847 was selected from DElncRNAs in human PBMCs between asthma patients and normal controls for further investigation. The expression levels of LINC00847 were quantified in PBMCs collected from 54 children with asthma exacerbation, 54 children with asthma remission, and 54 healthy children by real-time qPCR. The forced expiratory volume in the first second in percent predicted values (FEV1%), ratio of forced expiratory volume in 1 second to forced vital capacity (FEV1/FVC), and peak expiratory flow rate (PEF%) were tested for evaluation of lung function. The concentration of immunoglobulin E (IgE) and eosinophil count was examined. The serum levels of interleukin-4 (IL-4), interferon-γ (IFN-γ), and IL-17A were determined by the ELISA method. Results. The expression level of LINC00847 in PBMCs of asthma exacerbation children was remarkably higher than that in PBMCs of asthma remission children and healthy children ( p < 0.001 ); the expression level of LINC00847 in PBMCs of asthma remission children was notably higher than that in PBMCs of healthy children ( p < 0.001 ). Pearson correlation analysis revealed that the expression levels of LINC00847 in PBMCs of asthma children were negatively correlated with FEV1% (r = −0.489), FEV1/FVC (r = −0.436), PEF% (r = −0.626), and IFN-γ level (r = −0.614) of asthma children, but positively correlated with IgE concentration (r = 0.680), eosinophil count (r = 0.780), IL-4 (r = 0.524), and IL-17A (r = 0.622) levels. When LINC00847 expression was used to distinguish asthma exacerbation from asthma remission, a 0.871 AUC (95% CI: 0.805–0.936) was yielded with sensitivity of 79.63% and specificity of 77.78%. Conclusion. The study demonstrates that increased LINC00847 expression may be associated with the development and progression of asthma, possibly serving as a novel biomarker for predicting asthma exacerbation from asthma remission.

Rationale: Tocilizumab, an anti–interleukin-6 receptor antibody, had no statistically significant effect on skin sclerosis but preserved lung function over 48 weeks in patients with early systemic ...

The development of clinically progressive fibrosis complicates a wide array of interstitial lung diseases (ILDs). However, there are limited data regarding its prevalence and prognosis.We analysed consecutive patients seen for initial evaluation of a fibrosing form of ILD (FILD). Patients were evaluated for evidence of progressive fibrosis over the first 24 months of follow-up. We defined a progressive phenotype as the presence of at least one of the following: a relative decline in forced vital capacity (FVC) of ≥10%; a relative decline in FVC of ≥5%-10% with a relative decline in diffusing capacity of the lung for carbon monoxide of ≥15%, increased fibrosis on HRCT or progressive symptoms.Eight hundred and forty-four patients (397 with idiopathic pulmonary fibrosis [IPF] and 447 non-IPF FILD) made up the final analysis cohort. Three hundred and fifty-five patients (42.1%) met the progressive phenotype criteria (59.4% of IPF patients and 26.6% of non-IPF FILD patients, p 0.01). In both IPF and non-IPF FILD, transplantation-free survival differed between patients with a progressive phenotype and those without (p 0.01). Multivariable analysis showed that a progressive phenotype was an independent predictor of transplantation-free survival (hazard ratio [HR]: 3.36, 95% CI: 2.68-4.23, p 0.01). Transplantation-free survival did not differ between non-IPF FILD with a progressive phenotype and IPF (HR: 1.12, 95% CI: 0.85-1.48, p = 0.42).Over one-fourth of non-IPF FILD patients develop a progressive phenotype compared to approximately 60% of IPF patients. The survival of non-IPF FILD patients with a progressive phenotype is similar to IPF.

Background. Many studies have demonstrated that vitamin D has clinical benefits when used to treat patients with chronic obstructive pulmonary disease (COPD). However, most of these studies have insufficient samples or inconsistent results. The aim of this meta-analysis was to evaluate the effects of vitamin D therapy in patients with COPD. Methods. We performed a comprehensive retrieval in the following electronic databases: PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang Data, and Chinese Scientific Journals Database (VIP). Two trained reviewers identified relevant studies, extracted data information, and then assessed the methodical quality by the Cochrane risk of bias assessment tool, independently. Then, the meta-analyses were conducted by RevMan 5.4, binary variables were represented by risks ratio (RR), and continuous variables were represented by mean difference (MD) or standardized mean difference (SMD) to assess the efficacy of vitamin D therapy in patients with COPD. Then, publication bias assessment was conducted by funnel plot analysis. Finally, the quality of evidence was assessed by the GRADE system. Results. A total of 15 articles involving 1598 participants were included in this study. The overall results showed a statistical significance of vitamin D therapy in patients with COPD which can significantly improve forced expiratory volume in 1 second (FEV1) (MD: 5.69, 95% CI: 5.01-6.38, P < 0.00001 , I 2 = 51 % ) and FEV1/FVC (SMD:0.49, 95% CI: 0.39-0.60, P < 0.00001 , I 2 = 84 % ); and serum 25 (OH)D (SMD:1.21, 95% CI:1.07-1.34, P < 0.00001 , I 2 = 98 % ) also increase CD3+ Tcells (MD: 6.67, 95% CI: 5.34-8.00, P < 0.00001 , I 2 = 78 % ) and CD4+ T cells (MD: 6.00, 95% CI: 5.01-7.00, P < 0.00001 , I 2 = 65 % ); and T lymphocyte CD4+/CD8+ ratio (MD: 0.41, 95% CI: 0.20-0.61, P = 0.0001 , I 2 = 95 % ) obviously decrease CD8+ Tcells(SMD: -0.83, 95% CI: -1.05- -0.06, P < 0.00001 , I 2 = 82 % ), the times of acute exacerbation (RR: 0.40, 95% CI: 0.28-0.59, P < 0.00001 , I 2 = 0 % ), and COPD assessment test (CAT) score (MD: -3.77, 95% CI: -5.86 - -1.68, P = 0.0004 , I 2 = 79 % ). Conclusions. Our analysis indicated that vitamin D used in patients with COPD could improve the lung function (FEV1 and FEV1/FVC), the serum 25(OH)D, CD3+ T cells, CD4 + T cells, and T lymphocyte CD4+/CD8+ ratio and reduce CD8+ T cells, acute exacerbation, and CAT scores.

Background Individuals with COPD have increased sensitivity to traffic-related air pollution (TRAP) such as diesel exhaust (DE), but little is known about the acute effects of TRAP on exercise responses in COPD. Research question Does pre-exercise exposure to TRAP (DE300, PM2.5=300 μg/m3) have greater adverse effects on exercise endurance, exertional dyspnea, and cardiorespiratory responses to exercise in participants with mild-to-moderate COPD compared to former smokers with normal spirometry and healthy controls? Study design and Methods In this double-blind, randomized, placebo-controlled, crossover study, 11 healthy never-smokers, 9 ex-smokers without COPD and 9 ex-smokers with COPD were separately exposed to filtered air (FA) and DE300 for 2 hours separated by a minimum of 4 weeks. Participants performed symptom limited constant load cycling tests within 2.5 hours of exposure with detailed cardiorespiratory and exertional symptom measurements. Results There was a significant negative effect of TRAP on exercise endurance time in healthy controls (DE300 vs. FA: 10.2±8.2 vs. 12.9±9.5 min, respectively; p=0.03), but not in ex-smokers without COPD (10.1±6.9 vs. 12.2±8.0 min; respectively, p=0.57) or ex-smokers with COPD (9.8±6.4 vs. 8.4±6.6 min, respectively, p=0.31). Furthermore, significant increases in inspiratory duty cycle and absolute end-expiratory and end-inspiratory lung volumes were observed, and dyspnea ratings were elevated at select submaximal measurement times only in healthy controls. Interpretation Contrary to our hypothesis, it was the healthy controls rather than the ex-smokers with and without COPD that were negatively impacted by TRAP during exercise.

BACKGROUND: Emerging data from longitudinal studies suggest that preserved ratio impaired spirometry (PRISm), defined by proportionate reductions in FEV(1) and FVC, is a heterogeneous population with frequent transitions to other lung function categories relative to individuals with normal and obstructive spirometry. Controversy regarding the clinical significance of these transitions exists (eg, whether transitions merely reflect measurement variability or noise). RESEARCH QUESTION: Are individuals with PRISm enriched for transitions associated with substantial changes in lung function? STUDY DESIGN AND METHODS: Current and former smokers enrolled in the Genetic Epidemiology of COPD (COPDGene) study with spirometry available in phases 1 through 3 (enrollment, 5-year follow-up, and 10-year follow-up) were analyzed. Postbronchodilator lung function categories were as follows: PRISm (FEV(1) < 80% predicted with FEV(1)/FVC ratio ≥ 0.7), Global Initiative for Chronic Obstructive Lung Disease grade 0 (FEV(1) ≥ 80% predicted and FEV(1)/FVC ≥ 0.7), and obstruction (FEV(1)/FVC < 0.7). Significant transition status was affirmative if a subject belonged to two or more spirometric categories and had > 10% change in FEV(1) % predicted and/or FVC % predicted between consecutive visits. Ever-PRISm was present if a subject had PRISm at any visit. Logistic regression examined the association between significant transitions and ever-PRISm status, adjusted for age, sex, race, FEV(1) % predicted, current smoking, pack-years, BMI, and ever-positive bronchodilator response. RESULTS: Among subjects with complete data (N = 1,775) over 10.1 ± 0.4 years of follow-up, the prevalence of PRISm remained consistent (10.4%-11.3%) between phases 1 through 3, but nearly one-half of subjects with PRISm transitioned into or out of PRISm at each visit. Among all subjects, 19.7% had a significant transition; ever-PRISm was a significant predictor of significant transitions (unadjusted OR, 10.3; 95% CI, 7.9-13.5; adjusted OR, 14.9; 95% CI, 10.9-20.7). Results were similar with additional adjustment for radiographic emphysema and gas trapping, when lower limit of normal criteria were used to define lung function categories, and when FEV(1) alone (regardless of change in FVC % predicted) was used to define significant transitions. INTERPRETATION: PRISm is an unstable group, with frequent significant transitions to both obstruction and normal spirometry over time. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov; No.: NCT000608764; URL: www.clinicaltrials.gov

Background The effect of chronic sputum (CS) symptoms on health-related quality of life (HRQOL) in patients with nontuberculous mycobacterial pulmonary disease (NTM-PD) has not been studied. The aim of this study was to clarify the differences in the clinical characteristics of NTM-PD patients with and without CS and to investigate the effect of CS on HRQOL. Methods This cross-sectional study included patients with NTM-PD who were prescribed pulmonary rehabilitation at the Fukujuji Hospital from March 2016 to June 2019. HRQOL was evaluated using the MOS 36-Item Short-Form Health Survey (SF-36). Results Of the 99 subjects studied, 71 had CS (CS+) (71.7%), and 28 (28.3%) did not have CS (CS-). Patients in the CS + group had a lower body mass index, forced vital capacity percent predicted, and forced expiratory volume in 1 s percent predicted. Regarding the radiological evaluation, the proportion of patients with the fibrocavitary form and the radiological score were significantly higher in the CS + group. The mental component summary (MCS) score of the SF-36 were significantly lower in the CS + group. Multiple regression analysis showed that the presence of CS was independently associated with a lower MCS score of the SF-36. Conclusions NTM-PD patients with CS had more severe disease, with reduced pulmonary function and severe radiological findings. CS was shown to independently affect HRQOL, especially mental status.

Respiratory failure in Guillain-Barre syndrome (GBS) is common. Forced vital capacity (FVC) is the gold standard for monitoring respiratory muscle strength in GBS. In some clinical situations, FVC testing could be delayed or unavailable, thus there is a need for accurate, fast, and device-free bedside respiratory evaluation.We examined neck flexion strength in 23 GBS patients as a possible predictor of the need for subsequent intubation and as a predictor of FVC change.Intubation was required by 100% of patients with neck flexion strength of Medical Research Council grade ≤3. A correlation between neck flexion strength and FVC could not be determined.Significant weakness of neck flexion (Medical Research Council grade ≤3) at the time of admission correlates with poor respiratory status as measured by the need for intubation in patients with GBS.

Pectus excavatum is a frequent thoracic malformation increasingly treated with minimally invasive methods (MIRPE), which are performed for cardio-respiratory problems and in some centers also for esthetic considerations. Theoretically, MIRPE may increase thoracic elastic recoil, work of breathing and cause emphysema. The aim of the present study was to determine whether teenagers who underwent MIRPE may expect normal thoracic cage development, cardio-respiratory function, exercise capacity and asymptomatic functioning.Fifty five patients (21.1 ​± ​3.0 years) who underwent MIRPE between 2000 and 2010 were assessed 6.8 (±2.4) years after surgery. Controls were matched for sex, age and height to the intervention participants. Spirometry, body plethysmography, diffusion capacity and the 6 ​min walking test (6MWT) were performed. Anteroposterior (AP) and transverse chest diameters were measured.Participants who underwent MIRPE had normal pulmonary function, and exercise capacity. After adjustment for potential confounders, the intervention group had lower mean BMI [-1.88 ​± ​0.56 (kg/mYoung adults who undergo MIRPE may expect normal pulmonary function and exercise capacity. Observed differences in air trapping require further assessment in terms of emphysema development risk.

RATIONALE: In predominantly White populations, early chronic obstructive pulmonary disease (COPD) (i.e., COPD in people aged