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Background and objectives The highest incidence of death in systemic sclerosis due to pulmonary disease raises the need for early detection and treatment. The study aim is the assessment of interstitial pulmonary disease by Multi Detector High Resolution CT (MDCT) and finds its relationship with the other disease parameters and the Pulmonary Function tests (PFT). Patients and methods A prospective cross-sectional study was performed in Assiut University Hospitals from May 2018 to January 2020 and included 62 consecutive SSc female patients. Demographic, clinical, Laboratory, PFT and MDCT assessment were conducted for all participants. Results The coarseness of fibrosis was 8.32 (range 0.0–17), the average proportion of ground-glass opacification was 28.3% (range, 0.0%–75%). Honey-comb pattern was seen in (52.5%). Mean Extent of disease was 46.25 ± 3.7 (range 5–81). Restrictive deficit found in 42 patients. Significant relation was found between the extent of disease and the percentage predicted FVC (r = 0.373, p 0.018) and FEV1/FVC (r = 0.593, p 0.000) and coarseness of fibrosis and proportion of ground glass opacification correlated inversely with VC (r = −0.385, p = 0.014, r = −0.376, p = 0.017 respectively), Rayanud's phenomena, modified Rodnan Skin Score and Medsger's general are positively correlated with MDCT disease extent. Conclusion Scoring of systemic sclerosis (SSc) related interstitial lung disease (SSc-ILD) could be applicable as one of the important tools for disease assessment.

BackgroundRisk factors for COPD in high-income settings are well understood; however, less attention has been paid to contributors of COPD in low-income and middle-income countries (LMICs) such as pulmonary tuberculosis. We sought to study the association between previous tuberculosis disease and COPD by using pooled population-based cross-sectional data in 13 geographically diverse, low-resource settings.MethodsWe pooled six cohorts in 13 different LMIC settings, 6 countries and 3 continents to study the relationship between self-reported previous tuberculosis disease and lung function outcomes including COPD (defined as a postbronchodilator forced expiratory volume in one second (FEV1)/forced vital capacity (FVC) below the lower limit of normal). Multivariable regressions with random effects were used to examine the association between previous tuberculosis disease and lung function outcomes.ResultsWe analysed data for 12 396 participants (median age 54.0 years, 51.5% male); 332 (2.7%) of the participants had previous tuberculosis disease. Overall prevalence of COPD was 8.8% (range 1.7%–15.5% across sites). COPD was four times more common among those with previous tuberculosis disease (25.7% vs 8.3% without previous tuberculosis disease, p1(−0.70, 95% CI −0.84 to −0.55), FVC (−0.44, 95% CI −0.59 to −0.29) and the FEV1:FVC ratio (−0.63, 95% CI −0.76 to −0.51) when compared with those without previous tuberculosis disease.ConclusionsPrevious tuberculosis disease is a significant and under-recognised risk factor for COPD and poor lung function in LMICs. Better tuberculosis control will also likely reduce the global burden of COPD.

Rationale and Objectives To evaluate associations between longitudinal changes of quantitative CT parameters and spirometry in patients with fibrotic hypersensitivity pneumonitis (HP). Materials and Methods Serial CT images and spirometric data were retrospectively collected in a group of 25 fibrotic HP patients. Quantitative CT analysis included histogram parameters (median, interquartile range, skewness, and kurtosis) and a pretrained convolutional neural network (CNN)-based textural analysis, aimed at quantifying the extent of consolidation (C), fibrosis (F), ground-glass opacity (GGO), low attenuation areas (LAA) and healthy tissue (H). Results At baseline, FVC was 61(44-70) %pred. The median follow-up period was 1.4(0.8-3.2) years, with 3(2-4) visits per patient. Over the study, 8 patients (32%) showed a FVC decline of more than 5%, a significant worsening of all histogram parameters (p≤0.015) and an increased extent of fibrosis via CNN (p=0.038). On histogram analysis, decreased skewness and kurtosis were the parameters most strongly associated with worsened FVC (respectively, r2=0.63 and r2=0.54, p

Objective The organizing pneumonia (OP) pattern is the second most common finding in anti-synthase antibody syndrome (ASS), and nonspecific interstitial pneumonia (NSIP) is the most common finding. This study analysed the OP score changes by semiquantitative and quantitative analysis methods and the correlation between the high-resolution computed tomography (HRCT) indexes and the pulmonary function test parameters (PFTs) in ASS patients. Methods Data from ASS-OP patients admitted to the respiratory department of Ping Jin Hospital from October 2014 to June 2020 were retrospectively reviewed and analysed. Results Fourteen ASS-OP patients were recruited for this study. (1) In method-1, the consolidation (CO) score and the mean lung attenuation (MA) of poorly aerated and fibrosis lung fields (MAfibrosis) (r = 0.56, P = 0.04), the ground-glass opacity (GGO) score and the MA of non-aerated lung fields (MAnonaerated) (r = −0.64, P = 0.01), and the CO plus the GGO (CG) score and the MAnonaerated (r = −0.59, P = 0.03) of the lung fields had liner correlations. In method-2, the GGO score to the MAnonaerated (r = −0.58, P = 0.03), and the CG (r = −0.68, P = 0.01) score to the MAnonaerated had liner correlations. The FVC% (r = 0.68, P = 0.01) and FEV1% (r = 0.64, P = 0.01) to the MAfibrosis had good linear correlations. (2) Compared to the values before treatment, the CO pattern score, volume and weight percentages of the extracted whole lung volume with attenuation values of the nonaerated area (Vnonated%, Wnonaerated%), the volume of poorly aerated and fibrosis lung tissue (Vfibrosis%, Wfibrosis%), the weight percentages of normal aerated lung (Wnormal%), and the MAfibrosis exhibited significant differences during the 3–6 month follow-up period. Conclusion The GGO and CO scored by the semiquantitative or quantitative analysis methods was similar. The HRCT quantitative analysis parameters showed a good correlation with the PFTs in ASS-OP patients, can provide an accurate OP pattern interpretation, and may be used as a monitoring and therapeutic indicator for ASS-OP patients.

BACKGROUND Patients with chronic obstructive pulmonary disease (COPD) can develop left ventricular (LV) systolic dysfunction and geometric changes due to several reasons. We investigated subclinical LV systolic dysfunction and structural features in patients with COPD, and its correlation with the severity of airway obstruction, identified by GOLD classification. METHODS We studied 52 patients with COPD and 29 age and sex-matched controls, without any cardiac disease. In addition to conventional echocardiographic evaluation speckle tracking echocardiography (STE) based strain imaging were performed to analyze sub-clinical LV systolic dysfunction. Also LV volumes were measured by using three dimensional real time echocardiography (3DRTE). All patients underwent spirometry. RESULTS Conventional echocardiographic parameters (LV wall thickness and diameters, LV EF) and LV volume measurements were similar between the groups. LV global longitudinal peak systolic strain (-14.76 ± 2.69% to -20.27 ± 1.41%, p

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.

ZusammenfassungEine 70-jährige Patientin, die vor ca. 20 Jahren aufgrund einer Anti-Neutrophile cytoplasmatische Antikörper (ANCA)-positiven, rapid-progressiven Glomerulonephritis eine Nierentransplantation erhielt, wurde uns zur Abklärung einer fibrosierenden interstitiellen Lungenerkrankung mit Computertomografie (CT)-radiologischen Veränderungen im Sinne (i. S.) einer akuten Alveolitis zugewiesen. Sie beklagte eine bereits seit Längerem bestehende Belastungsdyspnoe. Lungenfunktionell zeigte sich eine leichte Restriktion (FVC 78% d. Soll), ausgeprägt eine schwere Diffusionsstörung (DLCO 41% d. Soll). Sowohl anamnestisch als auch serologisch ergab sich kein Hinweis auf eine exogen-allergische Alveolitis. In den bronchoskopisch gewonnenen Proben wurden initial Veränderungen i. S. einer nichtspezifischen interstitiellen Lungenerkrankung vom fibrotischen Typ, z. B. zu einer Reaktion im Rahmen der immunsuppressiven Therapie passend, gefunden. Mikrobiologisch wurde in der bronchoalveolären Lavage (BAL)-Flüssigkeit Herpes-simplex-Virus mittels Polymerase-Kettenreaktion (PCR) nachgewiesen. Unter der Arbeitsdiagnose einer Herpes-Pneumonitis wurde eine antivirale Therapie durchgeführt. Die immunsuppressive Therapie wurde fortgesetzt. In einer Kontrolle konnte der Herpesvirus nicht mehr nachgewiesen werden. Nach initialer subjektiver Verbesserung der Luftnot und wiederholter Kontroll-CT-Bildgebung stellten sich die initialen radiologischen Veränderung nach ca. einem Jahr als unverändert dar und die Belastungsluftnot als persistierend. In der neuerlichen transbronchialen Lungenbiopsie konnte eine metastatische pulmonale Kalzifikation nachgewiesen werden. Eine Aktivität der Erkrankung konnte erfreulicherweise ausgeschlossen werden. Fazit In der differenzialdiagnostischen Abklärung interstitieller Lungenerkrankungen muss v. a. bei Patient*innen mit vulnerablem Kalzium-Phosphat-Haushalt und Säure-Basen-Gleichgewicht, wie es z. B. im Rahmen chronischer Nierenerkrankungen auftritt, auch an die Möglichkeit einer metastatischen pulmonalen Kalzifikation (MPC) gedacht werden, v. a. wenn das radiologische Bild persistierende, oberlappenbetonte Milchglasveränderungen aufzeigt. Die Diagnosestellung erfordert hierbei eine multidisziplinäre Zusammenarbeit zwischen Pneumologen, Radiologen und Pathologen.

Background:Studies have associated HIV with an increased risk of obstructive lung disease (OLD). Objectives:We aimed to identify the predictive factors for impaired lung function in an urban, African, HIV-positive population. Method:A cross-sectional study was performed in Johannesburg, South Africa, from July 2016 to November 2017. A questionnaire was administered and pre- and post-bronchodilator spirometry conducted. The predictors investigated included age, sex, antiretroviral treatment (ART) duration, body mass index, history of tuberculosis (TB) or pneumonia, occupational exposure, environmental exposure, smoking and symptoms of OLD (cough, wheeze, mucus and dyspnoea). Impaired lung function was defined as a forced expiratory volume in 1 second/forced vital capacity (FEV1/FVC) ratio of < 0.70, or below the 20th percentile of normal. Results:The 98 ART-naïve participants (mean age = 34.0, standard deviation [s.d.] = 8.2), 85 participants on first-line ART (mean age = 36.9, s.d. = 6.6) and 189 participants on second-line ART (mean age = 43.5, s.d. = 7.9) were predominantly female (65.6%). Of the participants, 64 (17.2%) had impaired lung function and 308 had normal lung function. Linear regression identified age (β = –0.003,P< 0.01), male sex (β = –0.016,P= 0.03) and history of TB or pneumonia (β = –0.024,P< 0.01) as independent predictors of a lower FEV1/FVC ratio. Following logistic regression, only a history of TB or pneumonia (odds ratio = 2.58, 95% confidence interval = 1.47–4.52) was significantly related to impaired lung function (area under the receiver operating characteristic curve = 0.64). Conclusion:Our data show that a history of TB or pneumonia predicts impaired lung function. In order to improve timely access to spirometry, clinicians should be alert to the possibility of impaired lung function in people with a history of TB or pneumonia.

Increased fruit and vegetable consumption (FVC) beneficially impacts hypertension, yet researchers have not synthesized the effects of FVC interventions on blood pressure (BP) among overweight or obese individuals. Therefore, we aimed to examine if diets with increased FVC decrease BP in overweight and obese persons and explore effects of moderators, study methods, participants, intervention, and source characteristics.A thorough literature search was conducted in CINAHL, ProQuest DissertationTheses, Scopus, PubMed, The Cochrane Library, and Web of Science. Last search was conducted on February 28, 2020. Inclusion criteria consisted of randomized controlled trials, an increased FVC intervention, and a body mass index (BMI) ≥25. Studies were independently coded and evaluated for bias using Cochrane Collaboration's tool for assessing study bias. The Grading of Recommendations Assessment, Development and Evaluation tool was used to evaluate the body of evidence, which was found to be moderate. Data was analyzed using Stata 16SE Software. We used a random effects model, comparing mean differences. Moderator analysis was conducted using meta-regression for continuous variables and meta-analytic ANOVA analog for categorical variables. Publication bias was assessed using funnel plot symmetry, Begg and Mazumdar's rank and correlation, Egger's test of the intercept, and Duval and Tweedie's trim and fill.Ten studies met criteria, which included 6862 participants. Overall, effects of FVC interventions on systolic blood pressure (SBP) was 2.16 mmHg (p 0.001) and -0.55 mmHg (p = 0.39) for diastolic blood pressure (DBP). Moderator analyses showed greater drops in SBP from samples recruited from the community and medical schools (vs. health care/programs), interventions that used the DASH diet, and measured intake with food diaries. When concealed allocation was used and fidelity checked, there were less decreases in SBP than when it was not used. The amount of FVC significantly moderated the effects of SBP and DBP with greater increased FVC leading to greater decreases in SBP and DBP.Our findings are encouraging in that FVC improves blood pressure. However, outcomes are limited by the small number of studies that met inclusion criteria, significant heterogeneity, possible publication bias, and several studies had quality concerns. Tests for publication bias indicated none and most heterogeneity among studies was explained with moderator analysis our findings should be interpreted with caution.Increased FVC decreased SBP and DBP in obese and overweight individuals which may lower the risk of cardiovascular events. In the future, researchers might conduct higher quality studies and report quality indicators. Researchers might examine the effects of interventions for specific subgroups (overweight vs obese, younger vs older) and explore the impacts of diet-assisted technologies.

Background Respiratory and cardiovascular disease (CVD) frequently coexist; however, there is limited evidence on the relationship between chronic respiratory symptoms in young adulthood and late-onset CVD. Research Question Are chronic respiratory symptoms in young adulthood associated with CVD and all-cause mortality in later life? Study Design and Methods A total of 4,621 participants from CARDIA (Coronary Artery Risk Development in Young Adults) cohort study aged 18–30 were included. Chronic respiratory symptoms were identified through respiratory symptom questionnaires in two consecutive exams. Incident CVD and all-cause mortality were adjudicated over 30-year follow-up. Multivariable Cox proportional hazards models were used to explore association of chronic respiratory symptoms with incident CVD and all-cause mortality. Results During a median follow-up of 30.9 years, 284 CVD events (6.15%) and 378 deaths (8.18%) occurred. After multivariable adjustment for demographics, cardiovascular risk factors, smoking and lung function, the hazard ratios (95% CIs) for CVD events were 1.51 (1.18-1.93) for any respiratory symptom, 1.57 (1.18-2.09) for cough or phlegm, 1.31 (1.01-1.68) for wheeze, 1.73 (1.25-2.41) for shortness of breath, and 1.32 (1.01-1.71) for chest illnesses. Similar findings were also observed in all-cause mortality. Comparing 0 versus 3-4 respiratory symptoms, the hazard ratios (95% CIs) were 1.97 (1.34-2.91) for CVD and 1.75 (1.23-2.47) for all-cause mortality. Similar results were observed in various sensitivity analyses. Interpretation Chronic respiratory symptoms in young adulthood are associated with an increased risk of CVD and all-cause mortality in midlife independent of established cardiovascular risk factors, smoking and lung function. Identifying chronic respiratory symptoms in young adulthood may help provide prognostic information regarding future cardiovascular health.

Introduction: Asthma is defined as a chronic inflammatory airway disease. Recent studies have shown the association between metabolic syndrome and deterioration of lung functions in patients with asthma. The aim of this study was to evaluate the relationship between metabolic syndrome and asthma status. Methods: In this prospective cross-sectional study, 160 asthmatic patients attending Razi hospital in Guilan province were divided equally into two groups of 80 patients. The case group comprised asthmatic patient with metabolic syndrome and the control group involved asthmatic patient without metabolic syndrome. Blood pressure, height, weight, waist circumferences, fasting blood glucose and lipid profiles were measured by standard methods. Asthma severity was determined based on clinical symptoms and GINA criteria. To evaluate pulmonary function parameters, spirometry was performed for the patients. Results: Pulmonary function tests including FEF, FVC and FEV1 were significantly lower in the case group compared to the control group (P < 0.05). Also, a significant negative correlation was found between waist circumference, cardiovascular risk factors (including diabetes, hypertriglyceridemia, hypertension) with spirometric indices (P < 0.05). Conclusion: Metabolic syndrome causes major declines of pulmonary parameters in asthma patients; thus controlling metabolic syndrome might improve symptoms of asthma.

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.

Most pulmonary conditions reduce FVC, but studies of patients with combined pulmonary fibrosis and emphysema demonstrate that reductions in FVC are less than expected when these two conditions coexist clinically.Do interstitial lung abnormalities (ILAs), chest CT imaging findings that may suggest an early stage of pulmonary fibrosis in individuals with undiagnosed disease, affect the association between emphysema and FVC?Measures of ILA and emphysema were available for 9,579 and 5,277 participants from phases 1 (2007-2011) and 2 (2012-2016) of the Genetic Epidemiology of Chronic Obstructive Pulmonary Disease Study (COPDGene), respectively. ILA were defined by Fleischner Society guidelines. Adjusted linear regression models were used to assess the associations and interactions among ILA, emphysema, measures of spirometry, and lung function.ILA were present in 528 (6%) and 580 (11%) of participants in phases 1 and 2 of COPDGene, respectively. ILA modified the association between emphysema and FVC (P .0001 for interaction) in both phases. In phase 1, in those without ILA, a 5% increase in emphysema was associated with a reduction in FVC (-110 mL; 95% CI, -121 to -100 mL; P .0001); however, in those with ILA, it was not (-11 mL; 95% CI, -53 to 31; P = .59). In contrast, no interaction was found between ILA and emphysema on total lung capacity or on diffusing capacity of carbon monoxide.The presence of ILA attenuates the reduction in FVC associated with emphysema.

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.

Introduction: COPD is associated with several risk factors and co morbid conditions. Dealing with co-morbidity needs a patient centered approach, rather than a disease oriented approach7. The present study was conducted to study risk factors and co morbid conditions of COPD patients. Material and Methods: The present study was conducted in department of Pulmonary Medicine at Shri Ram Murti Smarak Institute of Medical Sciences with respiratory complaints over a period of one and a half year. The data was collected in terms of demographic features, anthropometric measurements and various risk factors and co morbid conditions. Spirometry was performed thrice and the largest values of both FVC and FEV1 were noted from three technically satisfactory curves. COPD severity was classified based on Spirometric assessment according to the GOLD classification. Categorical variables were analyzed using proportions and percentages. Results: In a study of 201 cases that were diagnosed as a case of COPD the mean age was 62.6 years and male predominance. Majority of the patients had sedentary life style and were from poor class. The co morbid conditions anemia, cardiac, hypertension, diabetes mellitus, lipid disorders, thyroid disorders, osteoporosis, psychiatric illness, ophthalmic defects and obstructive sleep apnea was found in 43.8%, 52.2%, 65.2%, 52.2%, 51.7%, 64.7%, 72.1%, 66.7%, 28.9% and 54.2% respectively. Conclusion: Co morbidities should be taken into consideration while prescribing multiple drugs so that side effects and interactions of drug can be monitored and quality of life can be improved.

Objective To evaluate the long-term safety and efficacy of indacaterol/glycopyrronium (IND/GLY) in patients with COPD in a real-world setting in Japan. Methods This 52-week, multicentre, post-marketing surveillance conducted in Japan between December 2013 and August 2019 included patients using IND/GLY for the first time to relieve airway obstructive disorder-related symptoms. Safety outcomes included the incidence of adverse events (AEs), serious AEs (SAEs), adverse drug reactions (ADRs), and serious ADRs during the 52-week period. The incidence of priority variables, including cardiovascular/cerebrovascular (CCV) AEs, β-adrenergic-related or anticholinergic AEs and cough, was also assessed. Safety outcomes were also evaluated in elderly patients. Efficacy outcomes included a physician's global assessment, COPD assessment test (CAT) and lung function test. Results Of the 1,167 patients registered, 1,108 were included in the safety and efficacy analysis. In the safety analysis population, the incidence of AEs was 13.54%, that of SAEs was 4.69%, that of ADR was 3.61%, and that of serious ADRs was 0.36% over 52 weeks. CCV AEs, β-adrenergic-related and anticholinergic AEs and cough were reported as 2.62%, 1.99% and 0.63%, respectively. The physician's global assessment showed that the overall response rate at the last assessment was 74.19%. The mean (95% confidence interval) CAT scores decreased from the start of treatment to Week 52 with IND/GLY (-6.9 [-7.8 to -6.1]). The lung function (FEV1 and FVC) improved over time from the start of IND/GLY to Week 52. Conclusion IND/GLY demonstrated a good long-term safety profile in a real-world setting in Japanese patients with COPD, with beneficial effects in terms of the lung function and symptoms in clinical use.

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 Bronchial thermoplasty is a device-based treatment for subjects ≥18 years with severe asthma poorly controlled with inhaled corticosteroids and long-acting beta-agonists. The Post-FDA Approval Clinical Trial Evaluating Bronchial Thermoplasty in Severe Persistent Asthma (PAS2) study collected data on severe asthmatics undergoing this procedure. Research Question What are the 5-year efficacy and safety results in severe asthmatics who have undergone bronchial thermoplasty? Study Design and Methods This was a prospective, open-label, observational, multi-center study conducted in the United States and Canada. Subjects aged 18-65, taking inhaled corticosteroids ≥1000μg/day (beclomethasone or equivalent) and long-acting β-agonists ≥80μg/day (salmeterol or equivalent) were included. Severe exacerbations, hospitalization, emergency department visits, and medication usage were evaluated for the 12 months prior to and at years 1-5 post-treatment. Spirometry was evaluated at baseline and at years 1-5 post-treatment. Results 284 subjects were enrolled at 27 centers; 227 subjects (80%) completed 5 years of follow-up. By year 5 post-treatment, the proportion of subjects with severe exacerbations, emergency department visits, and hospitalizations was 42.7%, 7.9%, and 4.8%, respectively, compared to 77.8%, 29.4%, and 16.1% in the 12 months prior to treatment. The proportion of subjects on maintenance oral corticosteroids decreased from 19.4% at baseline to 9.7% at 5 years. Analyses of subgroups based on baseline clinical and biomarker characteristics revealed a statistically significant clinical improvement among all subgroups. Interpretation Five years after treatment, subjects experienced decreases in severe exacerbations, hospitalizations, emergency department visits and corticosteroid exposure. All subgroups demonstrated clinically significant improvement, suggesting that bronchial thermoplasty improves asthma control in different asthma phenotypes.

Background Pirfenidone slows the progression of idiopathic pulmonary fibrosis. We investigated the efficacy and safety of pirfenidone by dose and disease severity in real-world patients with idiopathic pulmonary fibrosis.Methods This multi-centre retrospective cohort study investigated 338 patients treated with pirfenidone between July 2012 and March 2018. Demographics, pulmonary function, mortality, and pirfenidone-related adverse events were recorded. Efficacy was analysed according to pirfenidone dose and disease severity using linear mixed-effects models to assess the annual decline rate of forced vital capacity (FVC) and diffusing capacity (DL CO ) of the lungs for carbon monoxide.Results The mean %FVC predicted and %DL COpredicted were 72.6±13.1% and 61.4±17.9%, respectively. Pirfenidone treatment lasted 16.1±9.0 months. In the standard-dose (1800 mg/day) group, the mean %FVC predicted was -6.56% (95% CI -9.26, -3.87) per year pre-pirfenidone treatment, but -4.43% (95% CI -5.87, -3.00) per year post-treatment. In the lower-dose group, the mean %FVC predicted was -4.96% (95% CI -6.82, -3.09) per year pre-pirfenidone treatment, but -1.79% (95% CI -2.75, -0.83) per year post-treatment. The FVC decline rate was significantly reduced regardless of GAP stage. However, the DL CO decline rate was significantly reduced in the GAP stage II–III group, but not stage I group. Adverse events and mortality were similar across dose groups, but were more frequent in the GAP stage II–III group than in the stage I group.Conclusions The effect of pirfenidone on reducing disease progression persisted even with a consistent lower dose of pirfenidone.Trial registration Retrospectively registered

Background The adherence to and clinical efficacy of pulmonary rehabilitation in idiopathic pulmonary fibrosis (IPF), particularly in comparison to people with chronic obstructive pulmonary disease (COPD), remains uncertain. The objectives of this real-world study were to compare the responses of patients with IPF with a matched group of patients with COPD undergoing the same supervised, outpatient pulmonary rehabilitation program, and to determine whether pulmonary rehabilitation is associated with survival in IPF. Research question Do people with IPF improve to the same extent with pulmonary rehabilitation as a matched group of individuals with COPD, and are non-completion of and/or non-response to pulmonary rehabilitation associated with one-year all-cause mortality in IPF? Study design and methods Using propensity score matching, 163 patients with IPF were matched 1:1 with a control group of 163 patients with COPD referred to pulmonary rehabilitation. We compared between-group pulmonary rehabilitation completion rates and response. Survival status in the IPF cohort was recorded over one-year following pulmonary rehabilitation discharge. Cox proportional-hazards regression explored the association between pulmonary rehabilitation status and all-cause mortality. Results Similar pulmonary rehabilitation completion rates (IPF: 69%; COPD: 63%; p=0.24) and improvements in exercise response were observed in both groups with no significant mean (95% confidence interval (CI)) between-group differences in incremental shuttle walk (ISW) change (2 (-18 to 22) meters). Pulmonary rehabilitation non-completion (hazard ratio (HR) (95%CI) 5.62 (2.24 to 14.08)) and non-response (HR (95%CI) 3.91 (1.54 to 9.93)) were independently associated with increased one-year all-cause mortality in IPF. Interpretation Compared with a matched group of patients with COPD, this real-word study demonstrates that patients with IPF have similar completion rates and magnitude of response to pulmonary rehabilitation. In IPF, non-completion of and non-response to pulmonary rehabilitation were associated with increased all-cause mortality. These data reinforce the benefits of pulmonary rehabilitation in patients with IPF.

Using data from the SENSCIS trial, these analyses were undertaken to assess the effects of nintedanib versus placebo in subgroups of patients with systemic sclerosis-associated interstitial lung disease (SSc-ILD), based on characteristics previously identified as being associated with the progression of SSc-ILD.Patients with SSc-ILD were randomized to receive either nintedanib or placebo, stratified by anti-topoisomerase I antibody (ATA) status. We assessed the rate of decline in forced vital capacity (FVC) (expressed in ml/year) over 52 weeks in subgroups based on baseline ATA status, modified Rodnan skin thickness score (MRSS) (18 versus ≥18), and SSc subtype (limited cutaneous SSc [lcSSc] versus diffuse cutaneous SSc [dcSSc]).At baseline, 60.8% of 576 patients who received treatment with either nintedanib or placebo were positive for ATA, 51.9% had dcSSc, and 77.5% of 574 patients with MRSS data available had an MRSS of18. The effect of nintedanib versus placebo on reducing the rate of decline in FVC (ml/year) was numerically more pronounced in ATA-negative patients compared to ATA-positive patients (adjusted difference in the rate of FVC decline, 57.2 ml/year [95% confidence interval (95% CI) -3.5, 118.0] versus 29.9 ml/year [95% CI -19.1, 78.8]), in patients with a baseline MRSS ≥18 compared to those with a baseline MRSS of18 (adjusted difference in the rate of FVC decline, 88.7 ml/year [95% CI 7.7, 169.8] versus 26.4 ml/year [95% CI -16.8, 69.6]), and in patients with dcSSc compared to those with lcSSc (adjusted difference in the rate of FVC decline, 56.6 ml/year [95% CI 3.2, 110.0] versus 25.3 ml/year [95% CI -28.9, 79.6]). However, all exploratory interaction P values were nonsignificant (all P 0.05), indicating that there was no heterogeneity in the effect of nintedanib versus placebo between these subgroups of patients.In patients with SSc-ILD, reduction in the annual rate of decline in FVC among patients receiving nintedanib compared to those receiving placebo was not found to be heterogenous across subgroups based on ATA status, MRSS, or SSc subtype.

Background Interstitial lung abnormalities (ILA) may represent undiagnosed early-stage or subclinical interstitial lung disease (ILD). ILAs are often observed incidentally in patients who subsequently develop clinically overt ILD. There is limited information on consensus definitions for, and the appropriate evaluation of, ILA. Early recognition of patients with ILD remains challenging, yet critically important. Expert consensus could inform early recognition and referral. Research Question Can consensus-based expert recommendations be identified to guide clinicians in the recognition, referral, and follow-up of patients with or at risk of developing early ILDs? Study Design and Methods Pulmonologists and radiologists with expertise in ILD participated in two iterative rounds of surveys. The surveys aimed to establish consensus regarding ILA reporting, identification of patients with ILA, and identification of populations that might benefit from screening for ILD. Recommended referral criteria and follow-up processes were also addressed. Threshold for consensus was defined a priori as ≥ 75% agreement or disagreement. Results Fifty-five experts were invited and 44 participated; consensus was reached on 39 of 85 questions. The following clinically important statements achieved consensus: honeycombing and traction bronchiectasis or bronchiolectasis indicate potentially progressive ILD; honeycombing detected during lung cancer screening should be reported as potentially significant (eg, with the Lung CT Screening Reporting and Data System “S-modifier” [which indicates clinically significant or potentially significant noncancer findings]), recommending referral to a pulmonologist in the radiology report; high-resolution CT imaging and full pulmonary function tests should be ordered if nondependent subpleural reticulation, traction bronchiectasis, honeycombing, centrilobular ground-glass nodules, or patchy ground-glass opacity are observed on CT imaging; patients with honeycombing or traction bronchiectasis should be referred to a pulmonologist irrespective of FVC and diffusion capacity values; and patients with systemic sclerosis should be screened with pulmonary function tests for early-stage ILD. Interpretation Guidance for identifying clinically relevant ILA, with subsequent referral and follow-up, was established. These results lay the foundation for developing practical guidance on managing patients with ILA.

Chronic hypersensitivity pneumonitis (cHP) is a heterogeneous condition, where both small airway involvement and fibrosis may simultaneously occur. Computer-aided analysis of CT lung imaging is increasingly used to improve tissue characterization in interstitial lung diseases (ILD), quantifying disease extension, and progression. We aimed to quantify via a convolutional neural network (CNN) method the extent of different pathological classes in cHP, and to determine their correlation to pulmonary function tests (PFTs) and mosaic attenuation pattern.The extension of six textural features, including consolidation (C), ground glass opacity (GGO), fibrosis (F), low attenuation areas (LAA), reticulation (R) and healthy regions (H), was quantified in 27 cHP patients (age: 56 ± 11.5 years, forced vital capacity [FVC]% = 57 ± 17) acquired at full-inspiration via HRCT. Each class extent was correlated to PFTs and to mosaic attenuation pattern.H showed a positive correlation with FVC%, FEV1% (forced expiratory volume), total lung capacity%, and diffusion of carbon monoxide (DLCO)% (r = 0.74, r = 0.78, r = 0.73, and r = 0.60, respectively, p0.001). GGO, R and C negatively correlated with FVC% and FEV1% with the highest correlations found for R (r = -0.44, and r = -0.46 respectively, p0.05); F negatively correlated with DLCO% (r = -0.42, p0.05). Patients with mosaic attenuation pattern had significantly more H (p = 0.04) and lower R (p = 0.02) and C (p = 0.0009) areas, and more preserved lung function indices (higher FVC%; p = 0.04 and DLCO%; p = 0.05), but did not show more air trapping in lung function tests.CNN quantification of pathological tissue extent in cHP improves its characterization and shows correlation with PFTs. LAA can be overestimated by visual, qualitative CT assessment and mosaic attenuation pattern areas in cHP represents patchy ILD rather than small-airways disease.

Introduction Idiopathic pulmonary fibrosis (IPF) is progressive and irreversible. Some discrepancies about IPF staging exists, especially in mild phases. Forced vital capacity (FVC) higher than 80% has been considered early or mild IPF even for the design of clinical trials. Methods Spanish multicentre, observational, retrospective study of IPF patients diagnosed between 2012 and 2016, based on the ATS/ERS criteria, which presented FVC greater or equal 80% at diagnosis. Clinical and demographic characteristics, lung function, radiological pattern, treatment, and follow-up were analyzed. Results 225 IPF patients were included, 72.9% were men. The mean age was 69.5 years. The predominant high-resolution computed tomography (HRCT) pattern was consistent usual interstitial pneumonia (UIP) (51.6%). 84.7% of patients presented respiratory symptoms (exertional dyspnea and/or cough) and 33.33% showed oxygen desaturation below 90% in the 6 min walking test (6MWT). Anti-fibrotic treatment was initiated at diagnosis in 55.11% of patients. Median FVC was 89.6% (IQR 17) and 58.7% of patients had a decrease of diffusion lung capacity for carbon monoxide (DLCO) below 60% of theoretical value; most of them presented functional progression (61.4%) and higher mortality at 3 years (20.45%). A statistically significant correlation with the 3-years mortality was observed between DLCO Conclusions Patients with preserved FVC but presenting UIP radiological pattern and moderate–severe DLCO decrease at diagnosis associate an increased risk of progression, death or lung transplantation. Therefore, in these cases, preserved FVC would not be representative of early or mild IPF.

Serratus anterior plane block (SAPB) has been proven to be an efficient way to control postoperative pain. This study explored whether the use of continuous SAPB in combination with flurbiprofen could improve early pulmonary function in lung cancer patients undergoing video-assisted thoracoscopic surgery (VATS).From July 2019 to April 2020, patients who scheduled for elective lung resection undergoing VATS were randomly allocated to receive patient-controlled SAPB in combination with intravenous flurbiprofen or patient-controlled intravenous analgesia. Postoperative pulmonary function variables, including forced expiratory volume in 1 second, and forced vital capacity were collected before and 24, 48, and 72 hours after Surgical Procedure. Pain intensity was measured at rest and on coughing. Comfort scores during breathing exercises, postoperative pulmonary complications, and adverse events were recorded.A substantial reduction in lung function was exhibited in both groups after Surgical Procedure (P .001), but lung function variables in the continuous SAPB group were significantly higher (P .001) throughout the postoperative period up to 72 hours, regardless of the surgical procedure type. Meanwhile, there were significant differences of pain intensity at rest and on coughing between the groups (P .001). The incidence of pneumonia, pulmonary atelectasis, hypoxemia, vomiting, and the comfort score in the continuous SAPB group was significantly lower (P.05).Postoperative acute pain treatment with continuous SAPB in combination with flurbiprofen enhanced pulmonary function and reduced postoperative pulmonary complications in lung cancer patients undergoing VATS.

Background Riociguat is effective in delaying the time to clinical worsening (TCW) in patients with groups 1 and 4 pulmonary hypertension. Research Question Is riociguat more effective than placebo in prolonging TCW in sarcoidosis-associated pulmonary hypertension (SAPH)? Study Design and Methods This was a double-blind placebo-controlled trial. Patients with SAPH confirmed by right heart catheterization were randomized 1:1 to riociguat or placebo. Patients underwent 6-min walk distance (6MWD) and spirometry testing every 8 weeks. The primary end point was TCW, which was defined by the time to the first of the following: (1) all-cause mortality, (2) need for hospitalization because of worsening cardiopulmonary status attributable to progression of disease, (3) > 50 m decrease in the 6MWD test, or (4) worsening of World Health Organization functional class. Results A total of 16 patients were randomized to riociguat (n = 8) or placebo (n = 8). No difference was found in pulmonary artery mean, pulmonary vascular resistance, initial 6MWD, or FVC between the two groups. Five of eight patients who received placebo met TCW criteria, whereas none of the patients who received riociguat experienced a qualifying event. By log-rank analysis, patients who received riociguat were in the study for a significantly longer period (χ 2 = 6.259; P = .0124). The 6MWD decreased in the placebo group (median, –55.9 m; range, –176.8 to 60 m), but rose in the riociguat group (median, +42.7 m; range, –7.5 to +91.4 m; P = .0149), with a placebo-corrected difference of 94 m (P 30-m improvement in 6MWD (P > .05). No significant adverse events associated with riociguat occurred. Interpretation Over the 1 year of the study, riociguat was effective in preventing clinical worsening and improving exercise capacity in patients with SAPH. Trial Registry ClinicalTrials.gov ; No.: NCT02625558 ; URL: www.clinicaltrials.gov

AIMS Patients with type 2 diabetes mellitus (T2DM) have reduced vasodilatory responses during exercise partially attributable to low nitric oxide (NO) levels. Low NO contributes to greater α-adrenergic mediated vasoconstriction in contracting skeletal muscle. We hypothesized boosting NO bioavailability via 8wks of active beetroot juice (BRA, 4.03 mmol nitrate, 0.29 mmol nitrite, n = 19) improves hyperemia, via reduced α-mediated vasoconstriction, during handgrip exercise relative to nitrate/nitrite-depleted beetroot juice (BRP, n = 18) in patients with T2DM. METHODS Forearm blood flow (FBF) and vascular conductance (FVC) were calculated at rest and during handgrip exercise (20%max, 20contractions·min-1). Phenylephrine (α1-agonist) and dexmedetomidine (α2-agonist) were infused intra-arterially during independent trials to determine the influence of α-mediated vasoconstriction on exercise hyperemia. Vasoconstriction was quantified as the percent-reduction in FVC during α-agonist infusion, relative to pre-infusion, as well as the absolute change in %FVC during exercise relative to the respective rest trial (magnitude of sympatholysis). RESULTS ΔFBF (156 ± 69 to 175 ± 73 ml min-1) and ΔFVC (130 ± 54 to 156 ± 63 ml min-1·100 mmHg-1, both P

The aim of this Phase 1/2, 2-part, multicenter trial was to report clinical safety and efficacy of long-term golodirsen treatment among ambulatory patients with exon 53 skip-amenable Duchenne muscular dystrophy (DMD). Part 1 was a 12-week, randomized, double-blind, placebo-controlled, dose-titration study followed by 9-week safety review. Part 2 was a 168-week, open-label evaluation of golodirsen 30 mg/kg. Part 1 primary endpoint was safety. Part 2 primary endpoints were dystrophin protein expression and 6-minute walk test (6MWT); secondary endpoints were percent predicted forced vital capacity (FVC%p) and safety. Post hoc ambulation analyses used mutation-matched external natural history controls. All patients from Part 1 (golodirsen, n = 8; placebo, n = 4) plus 13 additional patients entered Part 2; 23 completed the study. Adverse events were generally mild, nonserious, and unrelated to golodirsen, with no safety-related discontinuations or deaths. Golodirsen increased dystrophin protein (16.0-fold; P