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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.

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.

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.

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 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

BACKGROUND/OBJECTIVE The aim of this study was to explore the associations between nailfold videocapillaroscopy (NVC) and pulmonary function tests (PFTs) in systemic sclerosis (SSc) patients. METHODS This was a longitudinal study with follow-up of unselected Brazilian SSc patients. Baseline clinical examination, serological workup, high-resolution chest tomography, and NVC were performed. Pulmonary function test was performed at baseline and after 24 months. Pulmonary function test worsening over time was defined as either a ΔFVC decline ≥10% or a ΔFVC decline ≥5% and

Background: Only a few studies directly compared the therapeutic efficacy and safety of two pressurized metered-dose inhalers (pMDIs) in asthma. We analyzed the asthma treatment outcomes, safety, and patient preferences using formoterol/beclomethasone (FORM/BDP), a pMDI with extra-fine particles, compared with formoterol/budesonide (FORM/BUD), another pMDI with non-extra-fine particles.Methods: In this randomized, double-blind, double-dummy parallel group study, 40 adult asthmatics were randomized to FORM/BDP group (n=18; active FORM/BDP and placebo FORM/BUD) or FORM/BUD group (n=22; active FORM/BUD and placebo FORM/BDP). During the two visits (baseline and end of 8-week treatment), subjects were asked to answer questionnaires including asthma control test (ACT), asthma control questionnaires (ACQ), and Quality of Life Questionnaire for Adult Korean Asthmatics (QLQAKA). Lung function, compliance with inhaler, and inhaler-handling skills were also assessed.Results: Ten subjects in the FORM/BDP group and 14 in the FORM/BUD group completed follow-up visits. ACT, ACQ, QLQAKA (a primary outcome), and adverse events did not differ between two groups. We found that the increase in forced expiratory volume in 1 second/forced vital capacity and forced expiratory flow at 25% to 75% of the pulmonary volume in the FORM/BDP group was higher than in the FORM/BUD group. Regarding preference, subjects responded that the flume velocity of FORM/BDP was higher, but more adequate than that of FORM/BUD. They also answered that FORM/BDP reached the trachea and bronchus and irritated them significantly more than FORM/BUD.Conclusion: The use of pMDI with extra-fine particles may relieve small airway obstruction more than the one with non-extra-fine particles despite no significant differences in overall treatment outcomes. Some asthmatics have a misconception about the adequacy of high flume velocity of pMDIs.

BACKGROUND Pulmonary rehabilitation (PR) has proven useful in patients with chronic obstructive pulmonary disease (COPD),but the benefits decrease over time. We evaluated the effects of a structured follow-up program after PR on patient pulmonary function, dyspnea, body composition, exercise capacity, quality of life, psychological status, i-BODE index, hospitalization status, 5-year survival rate. We explored whether this follow-up program could serve as a maintenance program. METHOD COPD patients who completed PR attended follow-up visits over 5 years. We administered incremental (ISWT), endurance shuttle walk tests (ESWT), measured body (BMI), fat-free mass indices (FFMI), recorded modified Medical Research Council (mMRC), St. George?s Respiratory Questionnaire (SGRQ), anxiety-depression scores. We also noted the forced expiratory volume in 1s (FEV1), the forced vital capacity (FVC), the forced mid-expiratory flow (FEF25-75), hospitalization, survival rates before, after PR, and in years 1, 2, 3, 5. This was a retrospective observational study. RESULTS Thirty-three COPD patients with a mean age of 58±8 years were enrolled. Twenty-seven (82%) were male. The mean FEV1 was 47±16% of the predicted. After PR, the mMRC scale, SGRQ, anxiety, depression scores; i-BODE index; ISWT, ESWT results improved (all p

Background: Advances in aerosol technology have improved drug delivery efficiency during noninvasive ventilation (NIV). Clinical evaluation of the efficacy of aerosol therapy during NIV in the treatment of acute exacerbation of chronic obstructive pulmonary disease (COPD) is very limited. The aim of our study was to compare the efficacy of bronchodilators administered through a vibrating mesh nebulizer (VMN) and jet nebulizer (JN) during NIV in patients with acute exacerbation of COPD. Methods: Prospective randomized cross-over study included 30 patients treated with NIV for acute exacerbation of COPD in an acute care hospital. Patients were consented and enrolled after stabilization of acute exacerbation (3-5 days after admission). Subjects were randomly assigned into two treatment arms receiving salbutamol (2.5 mg): with VMN (Aerogen Solo) and JN (Sidestream) positioned between the leak port and the nonvented oronasal mask during bilevel ventilation with a single-limb circuit. Measurements (clinical data, pulmonary function tests [PFTs], and arterial blood gases) were performed at baseline, 1, and 2 hours after treatment. Results: All measured PFT parameters significantly increased in both groups, but numerically results were better after inhalation with VMN than with JN: for forced expiratory volume in 1 second (FEV1) (mean increase from baseline to 120 minutes-165 ± 64 mL vs. 116 ± 46 mL, p = 0.001) and for forced vital capacity (FVC) (mean increase-394 ± 154 mL vs. 123 ± 57 mL, p < 0.001). There was also a statistically significant reduction in respiratory rate and in Borg dyspnea score after therapy with VMN in comparison with the conventional JN. In both groups, there were improvements in PaCO2, but with VMN these changes were significantly higher. Conclusion: Bronchodilator administration in patients with acute exacerbation of COPD during NIV with VMN resulted in clinically significant improvements in FVC and in Borg dyspnea score. Additional studies required to determine the impact on clinical outcomes.

Stem cell-based treatments have emerged as potentially effective approaches to delay the progression of amyotrophic lateral sclerosis (ALS). This study was designed as a single-center, prospective, and open-label study without a placebo control group to assess the safety and efficacy of concurrent intrathecal (IT) and intravenous (IV) administration of autologous bone marrow-derived mesenchymal stem cells (BM-MSCs) in patients with ALS. Autologous BM-MSCs were isolated and expanded under standard conditions. Fifteen patients were neurologically examined before BM-MSCs transplantation (1 × 10 6 cells/kg BW) to evaluate the rate of pre-treatment disease progression. To assess the safety and efficacy, patients were examined at 1, 3, and 6 months following the treatment with BM-MSCs. Adverse reactions were assessed, and the clinical outcome was determined by the evaluation of the ALS functional rating scale-revised (ALSFRS-R) and forced vital capacity (FVC). No serious adverse reaction was observed after combined IT and IV administration of BM-MSCs. The mean ALSFRS-R and FVC values remained stable during the first 3 months of the treatment. However, a significant reduction in ALSFRS-R and FVC levels was observed in these patients 6 months after BM-MSCs administration. Our study revealed that the concurrent IT and IV application of BM-MSCs in patients with ALS is a safe procedure. Furthermore, our data indicate a temporary delay in the progression of ALS after a single combined IT and IV administration of BM-MSCs. Further studies are required to explore if the repeated applications of BM-MSCs could prolong survival and delay the progression of ALS.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is associated with a poor prognosis with variable clinical course. Early identification of patients at high risk for disease progression and death would lead to early therapeutic intervention and thereby improvement of outcomes. Cold-inducible RNA-binding protein (CIRBP) is produced in response to cellular stresses, which is implicated in multiple biological processes, including cell survival and proliferation.RESEARCH QUESTION: Is CIRBP a useful biomarker for predicting the outcomes of patients with IPF?STUDY DESIGN AND METHODS: This study included 95 and 93 patients with IPF from two independent hospitals (derivation and validation cohorts, respectively). The association s of serum CIRBP level upon IPF diagnosis with disease progression within 1 year after diagnosis (i.e. ≥10% relative decline in percent predicted forced vital capacity or death) and all-cause mortality were retrospectively analysed. Discrimination performances for predicting these outcomes were evaluated using the c-index. RESULTS: Serum and lung tissue CIRBP levels were higher in patients with IPF than in control subjects. In the derivation cohort, the CIRBP high sub-group had significantly higher 1-year disease progression rates and lower cumulative survival rates than the CIRBP low sub-group, and the results were replicated in the validation cohort. In multivariate analyses, high serum CIRBP level was independently associated with higher 1-year disease progression and all-cause mortality rates in both cohorts. Combining the Gender-Age-Physiology and serum CIRBP models improved the c-indices for predicting 1-year disease progression and all-cause mortality compared with that of each model alone. The c-indices of serum CIRBP were particularly high in patients with Gender-Age-Physiology stage I.INTERPRETATION: This study successfully validated that serum CIRBP level was an independent predictor of 1-year disease progression and all-cause mortality in IPF. CIRBP is a promising biomarker that can help identify high-risk patients with IPF, especially in the early stage.

Asthma is one of the most common chronic diseases, which is a growing public health concern worldwide. In recent years, there has been an increasing number of interests in the relationship between vitamin D level and asthma control. Hence, the objective of this study was to assess the effect of high doses of vitamin D3 injection on asthmatic patient’s respiratory condition and quality of life. This was a single arm, before and after interventional study involving 18 patients with moderate to severe asthma. Spirometry test, St George’s respiratory questionnaire (SGRQ) and serum vitamin D assay were performed. Subjects with 25-hydroxyvitamin D3 (25-(OH) D3)

This study aimed to examine the effectiveness of high-intensity interval training (HIIT) on pulmonary function and exercise capacity in individuals with chronic obstructive pulmonary disease (COPD). Ten databases (PubMed, the Cochrane Library, Web of Science, EMBASE, MEDLINE, CINAHL, CNKI, Wanfang, Weipu, and CBM) were searched for relevant articles published from inception to 30 June 2020. Studies were included if they were randomized controlled trials (RCTs) comparing a HIIT group with usual care or other training groups. Quality was assessed using the Physiotherapy Evidence Database (PEDro) scale, and the overall quality of evidence was assessed using the GRADE approach. The primary outcomes were peak VO2 and FEV1% predicted, and the secondary outcomes were FEV1/FVC, peak VE, peak WR, 6MWD, dyspnea, health-related quality of life, and adverse event. Twelve articles (689 patients) were included. HIIT was shown to have a positive effect on exercise capacity (peak WR, 6MWD), pulmonary function (FEV1% pred, peak VE), dyspnea, and quality of life. However, sensitivity analyses for dyspnea were unstable, and the result changed from positive to negative after removing one study (SMD = − 0.13, 95% CI [− 0.44, 0.17], P = 0.40). HIIT could improve pulmonary function, exercise capacity, and quality of life but may not decrease dyspnea in patients with COPD. It can be recommended as a safe and effective exercise modality in rehabilitation programs. Given that the overall results were based on a limited number of studies with significant heterogeneity and some of the results were based on low GRADE rating evidence, more high-quality, larger sample size, multicenter, and long-term follow-up RCTs are needed to confirm the clinical efficacy of HIIT in patients with COPD. CRD42020165897.

Idiopathic pulmonary fibrosis (IPF) is a specific form of chronic, progressive, fibrosing interstitial pneumonia of unknown cause that leads to respiratory failure and death within few years of diagnosis. Pulmonary hypertension (PH) is a common complication in IPF, where it is strongly associated with increased morbidity and mortality. Patients with IPF and PH have particularly poor prognosis, despite current best medical therapies and the anti-fibrotic therapy with pirfenidone or nintedanib. The aim of our study was to assess the clinical and prognostic impact of PH in patients affected by IPF, already treated with pirfenidone or nintedanib. Seventy-four consecutive outpatients with a diagnosis of IPF, in therapy with pirfenidone or nintedanib, were prospectively enrolled in the study. All patients underwent pulmonary and cardiology assessment by clinical exam, spirometry, DLCO test, chest CT, 6MWT and echocardiography performed by a cardiologist experienced in PH in an ambulatory setting under resting conditions. GAP index has been determinate for all patients. During follow-up, all patients were evaluated every 6 months, or less if necessary. Data about mortality were then collected in a 3-year follow-up. Of the seventy-four patients enrolled, 38 were treated with pirfenidone and 36 with nintedanib. The two groups were comparable for age, gender, FVC, DLCO and PAPS. The patients were also divided in four groups, based on presence of mild/moderate/severe PH by echocardiography at baseline. Significant differences were found for DLCO and the GAP index. Severity of PH was significantly associated with a reduction of DLCO and with an increased GAP index. Survival was directly correlated with 6MWT (R = 0.48), DLCO (R = 0.29, p

Background: Spinal cord injury (SCI) is the injury of the spinal cord from the foramen magnum to the cauda equina which occurs as a result of compulsion, incision or contusion which is a life threatening condition that carries a high risk of morbidity and mortality. The Incidence of SCI varies from 9.2 to 56.1 per million. In the Indian setup, Approx. 20,000 new cases of SCI are added every year. Spinal cord injury (SCI) patients are at increased risk of chronic respiratory symptoms as Respiratory muscle paralysis both restricts maximum inflation of the lungs and impair the ability to cough. Patients with tetraplegia have decreased chest wall and lung compliance, rib cage stiffness with paradoxical chest wall movements. Material and method: A Pilot study was carried out on 04 Traumatic Spinal cord injury patients. The purpose of the study was To find out effectiveness of respiratory PNF on pulmonary functions (FVC & FEV1) & Chest Expansion in patients with spinal cord injury. The pulmonary Functions (FVC & FEV1) and chest expansion was measured by using Spirometer (PFT machine) and inch tape. The data was analyzed using standard statistical software. Result: In this study After 4 weeks of Intervention there was Significant Improvement in Pulmonary Functions ( Pre Mean of FEV1 & FVC 0.99 L & 1.03L and Post Mean of FEV1 & FVC was 1.25 L & 1.35L respectively) and Chest Expansion (Pre Mean was 1.15 cm and Post Mean was 1.62 cm at Xiphoid Process Level). Conclusion: This Study concluded that Respiratory PNF increases Pulmonary Functions and chest expansion in Patients with Spinal Cord Injury after 4 weeks of Intervention. Keywords: Spinal Cord Injury, Forced Expiratory Volume (FEV1), Forced vital Capacity, Peak expiratory flow rate, Respiratory Proprioceptive Neuromuscular Facilitation Technique.

Background: Asthma is a chronic life-threatening disease as the airways in the lungs often swollen or inflamed, which makes the airways very sensitive. So, the exposure to the environment in day-to-day life triggers asthma. Asthma can affect at any age group. This study mainly focuses on comparing the effects of Buteyko breathing technique and Pranayama on improving Pulmonary Function in subjects with Bronchial Asthma. Method: Total of 79subjects selected, out of those 66 subjects were included after obtaining the consent document. Subjects are divided into two groups by lottery method, in which 6 subjects dropped. So, the study was completed with 60 subjects. Both groups performed intervention for 1 hour a day 5 days week for 4 weeks. The outcomes of the study were FEV1, FVC & FEV1/FVC ratio. Results: Paired t test was used to assess statically significance between pre and post test scores with in the groups, independent t test was used to access statistical significance of post-test mean score between the groups, statistical analysis of the data revealed that Buteyko Breathing technique group has more difference when compare to Pranayama group. Conclusion: The results had shown that both Group-A (Buteyko Breathing Group) and Group-B (Pranayama Group) has improved significantly on pre and post-test values within the groups but when compared between the groups statistical significance is noted in Group-A. So, this study concludes that Group-A showed significant improvement on Pulmonary Function in subjects with Bronchial Asthma. Keywords: Buteyko Breathing technique, Nadishuddhi Pranayama, FEV1/FVC, Bronchial Asthma.

Summary Background INCREASE was a randomised, placebo-controlled, phase 3 trial that evaluated inhaled treprostinil in patients with interstitial lung disease (ILD) and associated pulmonary hypertension. Treprostinil improved exercise capacity from baseline to week 16, assessed with the use of a 6-min walk test, compared with placebo. Improvements in forced vital capacity (FVC) were also reported. The aim of this post-hoc analysis was to further characterise the effects of inhaled treprostinil on FVC in the overall study population and in various subgroups of interest. Methods In this post-hoc analysis, we evaluated FVC changes in the overall study population and in various subgroups defined by cause of disease or baseline clinical parameters. The study population included patients aged 18 years and older who had a diagnosis of ILD based on evidence of diffuse parenchymal lung disease on chest CT done within 6 months before random assignment (not centrally adjudicated). All analyses were done on the intention-to-treat population, defined as individuals who were randomly assigned and received at least one dose of study drug. The INCREASE study is registered with ClinicalTrials.gov, NCT02630316. Findings Between Feb 3, 2017, and Aug 30, 2019, 326 patients were enrolled in the INCREASE trial. Inhaled treprostinil was associated with a placebo-corrected least squares mean improvement in FVC of 28·5 mL (SE 30·1; 95% CI −30·8 to 87·7; p=0·35) at week 8 and 44·4 mL (35·4; −25·2 to 114·0; p=0·21) at week 16, with associated percentage of predicted FVC improvements of 1·8% (0·7; 0·4 to 3·2; p=0·014) and 1·8% (0·8; 0·2 to 3·4; p=0·028). Subgroup analysis of patients with idiopathic interstitial pneumonia showed FVC differences of 46·5 mL (SE 39·9; 95% CI −32·5 to 125·5; p=0·25) at week 8 and 108·2 mL (46·9; 15·3 to 201·1; p=0·023) at week 16. Analysis of patients with idiopathic pulmonary fibrosis showed FVC differences of 84·5 mL (52·7; −20·4 to 189·5; p=0·11) at week 8 and 168·5 mL (64·5; 40·1 to 297·0; p=0·011) at week 16. The most frequent adverse events included cough, headache, dyspnoea, dizziness, nausea, fatigue, and diarrhoea. Interpretation In patients with ILD and associated pulmonary hypertension, inhaled treprostinil was associated with improvements in FVC versus placebo at 16 weeks. This difference was most evident in patients with idiopathic interstitial pneumonia, particularly idiopathic pulmonary fibrosis. Inhaled treprostinil appears to be a promising therapy for idiopathic pulmonary fibrosis that warrants further investigation in a prospective, randomised, placebo-controlled study. Funding United Therapeutics Corporation.

Background Glutathione S-transferase omega-1 (GSTO1-1) is a cytosolic enzyme that modulates the S-thiolation status of intracellular factors involved in cancer cell survival or in the inflammatory response. Studies focusing on chronic obstructive pulmonary disease (COPD) have demonstrated that GSTO1-1 is detectable in alveolar macrophages, airway epithelium and in the extracellular compartment, where its functions have not been completely understood. Moreover GSTO1-1 polymorphisms have been associated with an increased risk to develop COPD. Against this background, the aim of this study was to evaluate GSTO1-1 levels and its polymorphisms in cystic fibrosis (CF) patients. Methods Clinical samples from a previous study published by our groups were analyzed for GSTO1-1 levels and polymorphisms. For comparison, a model of lung inflammation in CFTR-knock out mice was also used. Results Our data document that soluble GSTO1-1 can be found in the airways of CF patients and correlates with inflammatory parameters such as neutrophilic elastase and the chemokine IL-8. A negative correlation was found between GSTO1-1 levels and the spirometric parameter FEV1 and the FEV1/FVC ratio. Additionally, the A140D polymorphism of GSTO1-1 was associated with lower levels of the antiinflammatory mediators PGE2 and 15(S)-HETE, and with lower values of the FEV1/FVC ratio in CF subjects with the homozygous CFTR ΔF508 mutation. Conclusions Our data suggest that extracellular GSTO1-1 and its polymorphysms could have a biological and clinical significance in CF. Pathophysiological functions of GSTOs are far from being completely understood, and more studies are required to understand the role(s) of extracellular GSTO1-1 in inflamed tissues.

Introduction: Necrotizing pneumonia (NP) is a serious complication of community-acquired pneumonia characterised by the destruction of normal lung parenchyma. No study has evaluated the repercussions of the lung damage in the years following the episode. The aim of this study was to assess the long-term impact on lung function and respiratory symptoms in children hospitalised due to NP. Methods: We analysed outcomes in children given a diagnosis of NP between January 2003 and April 2016. We selected patients aged more than 4 years capable of undergoing a lung function test, that had been followed up for at least 2 years. The patients completed a respiratory questionnaire and underwent a lung function test. Results: We included a total of 24 patients (12 male). The median age at the time of diagnosis was 28 months, the median length of stay was 15 days, and 18 patients required pleural drainage. The mean duration of follow-up after NP was 8.75 years. During the evaluation, none of the patients exhibited asthma, cough, or exercise-induced symptoms. Three children had a second episode of pneumonia that did not require hospital admission. The spirometry results were the following (given as mean ± standard deviation): FEV1 Z-score, −0.47 ± 0.65; FVC Z-score, −0.56 ± 0.73; and FEV1/FVC Z-score, 0.19 ± 0.98. We found no evidence of obstructive pulmonary disease or restrictive patterns. Conclusions: The long-term outcomes of paediatric NP are good. However, patients exhibited mildly impaired lung function several years after the episode. We recommend follow-up of these patients due to potential impairments in lung function in adulthood. Resumen: Introducción: La neumonía necrotizante (NN) es una complicación grave de la neumonía adquirida en la comunidad caracterizada por la destrucción del parénquima pulmonar normal. Ningún estudio ha evaluado las consecuencias de este daño pulmonar en los años posteriores al episodio. El objetivo es investigar el impacto a largo plazo sobre la función pulmonar y los síntomas respiratorios en niños ingresados por NN. Métodos: Seguimiento de niños diagnosticados de NN desde enero-2003 hasta abril-2016. Se seleccionaron a los mayores de 4 años, capaces de realizar una función pulmonar, y un seguimiento durante más de 2 años. Los pacientes recibieron un cuestionario respiratorio y completaron una prueba de función pulmonar. Resultados: Se incluyeron 24 pacientes (12 hombres). La edad mediana en el momento del diagnóstico fue de 26 meses, 15 días de hospitalización y 18 pacientes necesitaron drenaje pleural. Los pacientes fueron seguidos durante un promedio de 8.75 años después de la NN. Durante la evaluación, ningún paciente tuvo asma, tos o sintomatología inducida por el ejercicio. Tres niños sufrieron una segunda neumonía, que no requirió hospitalización. Los resultados de la espirometría fueron (media ± desviación estándar): Z-score FEV1 −0.47 ± 0.65, Z-score FVC −0.56 ± 0.73, Z-score FEV1/FVC 0.19 ± 0.98. No hubo evidencia de enfermedad pulmonar obstructiva o patrones restrictivos. Conclusiones: Los resultados a largo plazo de la NN pediátrica son buenos. Sin embargo, los pacientes tienen una función pulmonar ligeramente disminuida varios años después del episodio. Es aconsejable hacer un seguimiento de estos pacientes debido a la posible disminución de la función pulmonar en edad adulta.

Summary Background We previously described the contributions of increased total airway mucin concentrations to the pathogenesis and diagnosis of the chronic bronchitic component of chronic obstructive pulmonary disease (COPD). Here, we investigated the relative contribution of each of the major airway gel-forming mucins, MUC5AC and MUC5B, to the initiation, progression, and early diagnosis of airways disease in COPD. Methods SPIROMICS was a multicentre, observational study in patients aged 40–80 years recruited from six clinical sites and additional subsites in the USA. In this analysis, MUC5AC and MUC5B were quantitated by stable isotope-labelled mass spectrometry in induced sputum samples from healthy never-smokers, ever-smokers at risk for COPD, and ever-smokers with COPD. Participants were extensively characterised using results from questionnaires, such as the COPD assessment test (CAT) and St George's Respiratory Questionnaire; quantitative CT, such as residual volume/total lung capacity ratio (RV/TLC) and parametric response mapping-functional small airway disease (PRM-fSAD); and pulmonary function tests, such as FEV1, forced vital capacity (FVC), and forced expiratory flow, midexpiratory phase (FEF25–75%). Absolute concentrations of both MUC5AC and MUC5B were related to cross-sectional (baseline, initial visit) and 3-year follow-up longitudinal data, including lung function, small airways obstruction, prospective acute exacerbations, and smoking status as primary outcomes. This study is registered with ClinicalTrials.gov (NCT01969344). Findings This analysis included 331 participants (mean age 63 years [SEM 9·40]), of whom 40 were healthy never-smokers, 90 were at-risk ever-smokers, and 201 were ever-smokers with COPD. Increased MUC5AC concentrations were more reliably associated with manifestations of COPD than were MUC5B concentrations, including decreased FEV1 and FEF25–75%, and increased prospective exacerbation frequency, RV/TLC, PRM-fSAD, and COPD assessment scores. MUC5AC concentrations were more reactive to cigarette smoke exposure than were MUC5B concentrations. Longitudinal data from 3-year follow-up visits generated a multivariate-adjusted odds ratio for two or more exacerbations of 1·24 (95% CI 1·04–1·47, p=0·015) for individuals with high baseline MUC5AC concentration. Increased MUC5AC, but not MUC5B, concentration at baseline was a significant predictor of FEV1, FEV1/FVC, FEF25–75%, and CAT score decline during the 3-year follow-up. Moreover, current smokers in the at-risk group showed raised MUC5AC concentrations at initial visits and decreased lung function over 3 years. By contrast, former smokers in the at-risk group showed normal MUC5AC concentrations at the initial visit and preserved lung function over 3 years. Interpretation These data indicate that increased MUC5AC concentration in the airways might contribute to COPD initiation, progression, exacerbation risk, and overall pathogenesis. Compared with MUC5B, greater relative changes in MUC5AC concentrations were observed as a function of COPD severity, and MUC5AC concentration seems to be an objective biomarker to detect disease in at-risk and pre-COPD individuals. These data suggest that MUC5AC-producing pathways could be potential targets for future therapeutic strategies. Thus, MUC5AC could be a novel biomarker for COPD prognosis and for testing the efficacy of therapeutic agents. Funding National Institutes of Health; National Heart, Lung, and Blood Institute.

Objectives: This study aimed at assessing asthma control using Global Initiative for Asthma (GINA) asthma assessment, and determining its relationship with lung function parameters among asthmatic children in Usmanu Danfodiyo University Teaching hospital, Sokoto. Materials and Methods: This was a cross-sectional study among 60 children with asthma diagnosed based on GINA guidelines. It was conducted over a period of 4 months. The GINA asthma control assessment was administered to assess asthma control. Lung function was done using a portable spirometer. Results: Males accounted for 58.3% of the study population with M: F of 1.4:1 and median age of 9.47 years, with majority from urban domicile (91.7%). Well-controlled asthma accounted for 50.0% while 35.0% had partly controlled asthma and 15.0% had poorly controlled asthma. The median FEV1/FVC among the study participants was 0.856 (IQR: 0.170). There was no relationship between asthma control and LF parameters (FEV1: r = 0.044, P = 0.736, FVC: r = 0.010, P = 0.941, FEV1/FVC: r = 0.122, P = 0.352, and PEFR: r = 0.015, P = 0.911). Conclusion: Majority of the study participants had well-controlled asthma and no relationship was found between asthma control and lung function. Thus, serial monitoring of LF in addition to uniformly agreed standardized assessment of asthma control is required to objectively evaluate asthma control in children.

In patients with IPF, this study aimed (i) to examine the relationship between serial change in CT parameters of lung volume and lung function, (ii) to identify the prognostic value of serial change in CT parameters of lung volume, and (iii) to define a threshold for serial change in CT markers of lung volume that optimally captures disease progression. Serial CTs were analysed for progressive volume loss or fibrosis progression in 81 IPF patients (66 males, median age = 67 years) with concurrent forced vital capacity (FVC) (median follow-up 12 months, range 6–23 months). Serial CT measurements of volume loss comprised oblique fissure posterior retraction distance (OFPRD), aortosternal distance (ASD), lung height corrected for body habitus (LH), and automated CT-derived total lung volumes (ALV) (measured using commercially available software). Fibrosis progression was scored visually. Serial changes in CT markers and FVC were compared using regression analysis, and evaluated against mortality using Cox proportional hazards. There were 58 deaths (72%, median survival = 17 months). Annual % change in ALV was most significantly related to annual % change in FVC (R2 = 0.26, p

Objectives Inhaled recombinant human deoxyribonuclease (dornase alfa) and osmotic agents such as inhaled mannitol are used for improving the clearance of secretions of cystic fibrosis (CF) patients. We aimed to evaluate the long-term clinical effects of adding dry powder inhaled (DPI) mannitol in subjects with CF who are taking daily dornase alfa. Method We conducted a retrospective case-control study on subjects with CF. The effect of DPI mannitol was assessed by comparing DPI mannitol and dornase alfa combination with daily dornase alfa alone in children with CF during a 12-month period. The primary outcome measures of the study were absolute changes in percent predicted forced expiratory volume in 1 s (FEV1) and FEV1 z-scores and the secondary outcomes included other spirometry indices, body mass index, frequency of pulmonary exacerbations, SPO2 , and sputum microbiology. Result Of a total of 28 patients who committed to use DPI mannitol treatments during the study period, five had a positive challenge with DPI mannitol and two were aged over 18 years. Therefore, the mannitol treatment group consisted of 21 patients. However, the effect of DPI mannitol was analyzed using 15 patients in the mannitol treatment group who received DPI mannitol for at least 12 months, and 18 patients who only used dornase alfa constituted the control group. The median absolute change in FEV1 between baseline and the third month; and baseline and the 12th month were significantly higher in the mannitol treatment group (p = 0.038, p = 0.004, respectively). When the groups are compared with respect to absolute z-score changes, all spirometry indices, except FVC at the end of 3 months, showed statistically significant improvements in the mannitol treatment group. Some secondary outcomes like pulmonary exacerbation frequency during the study year and median absolute body mass index z-score changes from baseline to the end of the study showed no significant differences between the groups (p = 0.735, p = 0.161, respectively). No colonization changes were observed in the treatment group. Conclusions This study showed that in those patients who tolerated long-term (12 months) treatment with DPI mannitol and dornase alfa made greater improvements in FEV1, FVC, FEV1/FVC, FEF25-75 z-scores than treatment with dornase alfa alone in children with CF.

International audience; Introduction/aims: Respiratory status is a key determinant of prognosis in patients with Duchenne muscular dystrophy (DMD). We aimed to evaluate the determinants of diaphragm ultrasound and its performance in predicting restrictive respiratory patterns in DMD.Methods: This was a retrospective study of DMD patients followed in our center and admitted for an annual checkup from 2015 to 2018. We included DMD patients who underwent diaphragm ultrasound and pulmonary functional tests.Results: This study included 74 patients with DMD. The right diaphragm thickening fraction (TF) was significantly associated with age (P = .001), Walton score (P = .012), inspiratory capacity (IC) (P = .004), upright forced vital capacity (FVC) (P < .0001), supine FVC (P = .038), and maximal inspiratory pressure (MIP) (P = .002). Right diaphragm excursion was significantly associated with age (P < .0001), steroid use (P = .008), history of spinal fusion (P < .0001), body mass index (BMI) (P = .002), Walton score (P < .0001), IC (P < .0001), upright FVC (P < .0001), supine FVC (P < .0001), and MIP (P < .0001). A right diaphragm TF >28% and a right diaphragm excursion>25.4 mm were associated with an FVC >50% with, respectively, an area under the curve (AUC) of 0.95 (P = .001) and 0.93 (P < .001). A left diaphragm TF >26.8% and a left diaphragm excursion >21.5 mm were associated with an FVC >50% with, respectively, an AUC of 0.95 (P = .011) and 0.97 (P < .001).Discussion: Diaphragm excursion and diaphragm TF can predict restrictive pulmonary insufficiency in DMD.

OBJECTIVES Contemporary lower-field magnetic resonance imaging (MRI) may offer advantages for lung imaging by virtue of the improved field homogeneity. The aim of this study was to evaluate the utility of lower-field MRI for combined morphologic imaging and regional lung function assessment. We evaluate low-field MRI in patients with lymphangioleiomyomatosis (LAM), a rare lung disease associated with parenchymal cysts and respiratory failure. MATERIALS AND METHODS We performed lung imaging on a prototype low-field (0.55 T) MRI system in 65 patients with LAM. T2-weighted imaging was used for assessment of lung morphology and to derive cyst scores, the percent of lung parenchyma occupied by cysts. Regional lung function was assessed using oxygen-enhanced MRI with breath-held ultrashort echo time imaging and inhaled 100% oxygen as a T1-shortening MR contrast agent. Measurements of percent signal enhancement from oxygen inhalation and percentage of lung with low oxygen enhancement, indicating functional deficits, were correlated with global pulmonary function test measurements taken within 2 days. RESULTS We were able to image cystic abnormalities using T2-weighted MRI in this patient population and calculate cyst score with strong correlation to computed tomography measurements (R = 0.86, P < 0.0001). Oxygen-enhancement maps demonstrated regional deficits in lung function of patients with LAM. Heterogeneity of oxygen enhancement between cysts was observed within individual patients. The percent low-enhancement regions showed modest, but significant, correlation with FEV1 (R = -0.37, P = 0.007), FEV1/FVC (R = -0.33, P = 0.02), and cyst score (R = 0.40, P = 0.02). The measured arterial blood ΔT1 between normoxia and hyperoxia, used as a surrogate for dissolved oxygen in blood, correlated with DLCO (R = -0.28, P = 0.03). CONCLUSIONS Using high-performance 0.55 T MRI, we were able to perform simultaneous imaging of pulmonary structure and regional function in patients with LAM.

PURPOSE Whether the modified shuttle test (MST) achieves maximal effort in children and adolescents with asthma is unclear. The aim was to compare the physiological responses of MST to the cardiopulmonary exercise test (CPET) in pediatric patients with asthma, to observe its convergent validity. PATIENTS AND METHODS A cross-sectional study with volunteers with asthma (6-17 years of age) under regular treatment. The MST is an external-paced test, and the participants were allowed to walk/run. CPET was performed on a cycle ergometer to compare with MST. Gas exchange (VO2 , VCO2 , and VE) and heart rate (HR) were the outcomes and were continuously assessed in both tests. RESULTS Forty-seven volunteers were included, normal lung function expiratory forced volume at 1st second/forced vital capacity (FEV1 /FVC) 88.6 (7.7). VO2peak was higher at MST (2.0 ± 0.6 L/min) compared to CPET (1.6 ± 0.5 L/min), p

Methacholine challenge testing (MCT) is considered when asthma remains clinically suspected despite normal spirometry. Few studies have attempted to determine the predictive factors of MCT results. We aimed to establish which demographic data, clinical symptoms, pulmonary function testing results, and laboratory values were associated with abnormal MCT (provocation concentration causing a 20% decrease in FEVsub1/sub(PC20) ≤ 16 mg/mL) in subjects without airflow obstruction on spirometry.All patients who completed MCT at Montfort Hospital between January 1supst/sup, 2016 and December 31supst/sup, 2018 were identified. Subjects with a reduced FEVsub1/sub/FVC ratio were excluded. We used Pearson's chi-squared test and point-biserial correlation method to determine which variables had a significant relationship (ip/i lt; 0.05) with MCT results.23.3% of patients who underwent MCT had airflow limitation. In the 1126 subjects with a normal FEVsub1/sub/FVC ratio, PC20 ≤ 16 mg/mL was found in 13.0%. Younger age, female gender, body mass index ≥ 40, and reported wheezing were factors associated with increased probability of airway hyper responsiveness. Lower FEVsub1/sub, significant improvement of the FEVsub1/subpost-bronchodilator, reduced FEF25%-75%, greater FEF25%-75% reversibility, airway resistance measurements above the upper limit of normal, and increased blood eosinophil counts were predictive of abnormal MCT.Only 13.0% of patients referred for MCT had a PC20 ≤ 16 mg/mL when the FEVsub1/sub/FVC ratio was normal, highlighting the need to further define in which individuals this test is truly warranted. Further investigation is required to develop an easy-to-use and validated prediction model in order to better understand patients' pretest probability of abnormal MCT.

BACKGROUND Ultrasonography (USG) of the diaphragm is a promising alternative to pulmonary function tests (PFT) for assessing respiratory function in amyotrophic lateral sclerosis/motor neuron disease (ALS/MND). METHODS We studied 33 patients fulfilling Awaji criteria (definite = 14; probable = 12; possible = 7) and 33 age and gender-matched controls. Diaphragm thickness was measured using USG at the end of expiration (DTex) and end of inspiration (DTin). The thickness ratio (TR) was calculated as DTin/DTex. The mean age at onset and duration were 49.73 ± 12.7 years and 13.57 ± 9.7 months, respectively. Men = 25 (75.8%); Limb onset ALS/MND = 24 patients (72.7%); bulbar onset = 9 (27.3%). RESULTS Compared to controls, ALS/MND patients had reduced mean DTex (2.22 ± 0.29 mm vs. 2.02 ± 0.32 mm, p = .012) and DTin (4.0 ± 0.71 mm vs. 3.41 ± 0.38 mm, p

OBJECTIVES In epidemiological studies, childhood asthma is usually assessed with questionnaires directed at parents or children, and these may give different answers. We studied how well parents and children agreed when asked to report symptoms of wheeze and investigated whose answers were closer to measurable traits of asthma. METHODS LuftiBus in the school is a cross-sectional survey of respiratory health among Swiss schoolchildren aged 6-17 years. We applied questionnaires to parents and children asking about wheeze and exertional wheeze in the past year. We assessed agreement between parent-child answers with Cohen's kappa (k), and associations of answers from children and parents with fractional exhaled nitric oxide (FeNO) and forced expiratory volume in 1 s over forced vital capacity (FEV1 /FVC), using quantile regression. RESULTS We received questionnaires from 3079 children and their parents. Agreement was poor for reported wheeze (k = 0.37) and exertional wheeze (k = 0.36). Median FeNO varied when wheeze was reported by children (19 ppb, interquartile range [IQR]: 9-44), parents (22 ppb, IQR: 12-46), both (31 ppb, IQR: 16-55), or neither (11 ppb, IQR: 7-19). Median absolute FEV1 /FVC was the same when wheeze was reported by children (84%, IQR: 78-89) and by parents (84%, IQR: 78-89), lower when reported by both (82%, IQR: 78-87), and higher when reported by neither (87%, IQR: 82-91). For exertional wheeze findings were similar. Results did not differ by age or sex. CONCLUSION Our findings suggest that surveying both parents and children and combining their responses can help us to better identify children with measurable asthma traits.