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Background and Study Aim. In modern sports, the research and study of the functional capabilities of athletes' breathing is relevant. The analysis of individual results made it possible to form an idea about the respiratory functions of athletes. Among elite athletes, parameters of respiratory functions are significantly higher than the norm, so their interpretation relative to the general healthy population is inadequate. The purpose of the study is to determine lung volumes and dynamic parameters of the respiratory act and their difference in height and weight categories, respectively. Material and methods. The study involved 22 elite athletes aged 19-24 took part in the study. Testing of all athletes was carried out during the period of preparation for the competition The following research methods were used: method of anthropometry; method of computer Spirometry (was used to assess the functional state of reserve possibilities of the external breathing of athletes by absolute indicators). The studied material was processed by the methods of mathematical statistics using the "Statistica 6.0" software and MS Excel. Athletes were divided into three groups of height categories: group-A (190 cm and above), group-B (180-189 cm), group-C (170-179 cm) and three weight categories: group-D (90 kg and above), group-E (80-89 kg), group-F (70-79 kg). Results. Studies have shown that the absolute values of respiratory functions in athletes with significant hight and significant body weight are higher than in athletes with short height and insignificant weight. Real indicators of respiratory functions in most athletes are within the normal range. The highest actual indicators of respiratory functions are observed in the group of athletes with average height and average body weight. Also, in elite athletes with average height and average body weight, individual actual indicators are practically the same. Conclusion. Planning and construction of the training process requires knowledge of absolute and actual indicators of respiratory functions. The conducted research made it possible to establish the level of functional reserves of power and mobilization functions of breathing in elite-level rowers. The results allow effective planning of physical activity during training., Передумови та мета дослідження. У сучасному спорті актуальним є дослідження та вивчення функціональних можливостей дихання спортсменів. Аналіз індивідуальних результатів дав змогу скласти уявлення про дихальні функції спортсменів. Серед висококваліфікованих спортсменів показники респіраторних функцій значно вищі за норму, тому їх інтерпретація відносно загальної здорової популяції є неадекватною. Мета дослідження – визначити легеневі об’єми та динамічні параметри дихального акту та їх різницю у зростовій та ваговій категоріях відповідно.Матеріал і методи. У дослідженні взяли участь 22 елітних спортсмени віком 19-24 роки. Тестування всіх спортсменів проводилося в період підготовки до змагань. Використовувалися такі методи дослідження: метод антропометрії; метод комп’ютерної спірометрії (застосовувався для оцінки функціонального стану резервних можливостей зовнішнього дихання спортсменів за абсолютними показниками). Досліджуваний матеріал оброблено методами математичної статистики з використанням програмного забезпечення «Statistica 6.0» та MS Excel. Спортсмени поділялися на три групи зростових категорій: група-А (190 см і вище), група-Б (180-189 см), група-С (170-179 см) і три вагові категорії: група-D (90 кг і вище), група-Е (80-89 кг), група-F (70-79 кг).Результати. Дослідження показали, що абсолютні значення дихальних функцій у спортсменів зі значним зростом і значною масою тіла вищі, ніж у спортсменів з невисоким зростом і незначною вагою. Реальні показники дихальних функцій у більшості спортсменів знаходяться в межах норми. Найвищі фактичні показники дихальних функцій спостерігаються в групі спортсменів із середнім зростом і середньою масою тіла. Також у спортсменів із середнім зростом і середньою масою тіла індивідуальні фактичні показники практично однакові.Висновок. Планування і побудова тренувального процесу вимагає знання абсолютних і фактичних показників функцій дихання. Проведені дослідження дали змогу встановити рівень функціональних резервів силових та мобілізаційних функцій дихання у веслувальників елітного рівня. Результати дозволяють ефективно планувати фізичне навантаження під час тренування.

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 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.

Objectives: To determine the cardiovascular risk burden rehabilitation discharge, and explore the association between recovery during rehabilitation and CVD-risk profile. Methods: We included adults without CVD history admitted for rehabilitation. We evaluated rehabilitation outcomes on admission and discharge. CVD-risk was assessed by Framingham risk score (FRS), high-density lipoprotein (HDL), and fasting glucose level. Results: We analyzed data from 706 participants (69.55% men) with median age of 53.5 years. The median time-since-injury was 14 days and the admission length was 5.2 months. Majority had paraplegia (53.26%), and motor incomplete injury (53.68%). One-third of the cohort had high cardiovascular risk profile pre-discharge. At discharge, poorer anthropometric measures were associated with higher FRS and lower HDL levels. Individuals with higher forced vital capacity (>2.72 L) and peak expiratory flow (>3.4 L/min) had 0.16 mmol/L and 0.14 mmol/L higher HDL compared to those with lower respiratory function, respectively. Individuals with higher mobility score (>12.5) and functional independence score (>74) had 0.21 mmol/L and 0.18 mmol/L higher HDL compared to those with lower scores. Conclusion: There is high cardiometabolic syndrome burden and CVD-risk upon rehabilitation discharge. Higher respiratory function, mobility, and overall independence were associated with better CVD profile, although with study design limitations and short follow-up. Future studies should explore whether rehabilitation outcomes could be used to prioritize screening., + ID der Publikation: unilu_68449 + Sprache: Englisch + Letzte Aktualisierung: 2023-06-30 11:55:35

BACKGROUND The knowledge regarding the control of breathing during wakefulness in patients affected by obstructive sleep apnoea (OSAS) is still challenging. The aim of this study is firstly to analyse hypoxic and hypercapnic ventilatory response in OSA patients in comparison to controls and secondly, to investigate correlations between chemosensivity and both lung function tests, such as arterial blood gas analysis and spirometric parameters, and clinical characteristics, such as age and BMI. METHODS 17 never treated OSA patients (16M; 53±13.2 yrs; BMI= 34.5±8.1; AHI =45 ±14.7) underwent nocturnal cardiopulmonary monitoring test, complete lung function tests (spirometry , lung volumes and arterial blood gas analysis on room air). Read's rebreathing test was used to evaluate hypercapnic ventilatory response (HVRCO2); hypoxic ventilatory response (HVRO2) was studied through progressive and transient methods. The response was expressed in terms of slope of linear regression for HVRCO2 and of hyperbolic curve for HVRO2 between minute ventilation (VE) or mean inspiratory flow (VT/Ti) and PetCO2 or PetO2. RESULTS the OSA group showed increased transient, but not progressive, HVRO2 and a lower HVRCO2. A lower HVRCO2 was predicted by greater values of BMI (p

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.

Aims With interest in normal tissue sparing and dose-escalated radiotherapy in the treatment of inoperable locally advanced non-small cell lung cancer, this study investigated the impact of motion-managed moderate deep inspiration breath hold (mDIBH) on normal tissue sparing and dose-escalation potential and compared this to planning with a four-dimensional motion-encompassing internal target volume or motion-compensating mid-ventilation approach. Materials and methods Twenty-one patients underwent four-dimensional and mDIBH planning computed tomography scans. Internal and mid-ventilation target volumes were generated on the four-dimensional scan, with mDIBH target volumes generated on the mDIBH scan. Isotoxic target dose-escalation guidelines were used to generate six plans per patient: three with a target dose cap and three without. Target dose-escalation potential, normal tissue complication probability and differences in pre-specified dose-volume metrics were evaluated for the three motion-management techniques. Results The mean total lung volume was significantly greater with mDIBH compared with four-dimensional scans. Lung dose (mean and V21 Gy) and mean heart dose were significantly reduced with mDIBH in comparison with four-dimensional-based approaches, and this translated to a significant reduction in heart and lung normal tissue complication probability with mDIBH. In 20/21 patients, the trial target prescription dose cap of 79.2 Gy was achievable with all motion-management techniques. Conclusion mDIBH aids lung and heart dose sparing in isotoxic dose-escalated radiotherapy compared with four-dimensional planning techniques. Given concerns about lung and cardiac toxicity, particularly in an era of consolidation immunotherapy, reduced normal tissue doses may be advantageous for treatment tolerance and outcome.

Cardiac toxicity is a well-recognized risk after radiation therapy (RT) in patients with non-small cell lung cancer (NSCLC). However, the extent to which treatment planning optimization can reduce mean heart dose (MHD) without untoward increases in lung dose is unknown.Retrospective analysis of RT plans from 353 consecutive patients with locally advanced NSCLC treated with intensity modulated RT (IMRT) or 3-dimensional conformal RT. Commercially available machine learning-guided clinical decision support software was used to match RT plans. A leave-one-out predictive model was used to examine lung dosimetric tradeoffs necessary to achieve a MHD reduction.Of all 232 patients, 91 patients (39%) had RT plan matches showing potential MHD reductions of4 to 8 Gy without violating the upper limit of lung dose constraints (lung volume [V] receiving 20 Gy (V20 Gy)37%, V5 Gy70%, and mean lung dose [MLD]20 Gy). When switching to IMRT, 75 of 103 patients (72.8%) had plan matches demonstrating improved MHD (average 2.0 Gy reduction, P.0001) without violating lung constraints. Examining specific lung dose tradeoffs, a mean ≥3.7 Gy MHD reduction was achieved with corresponding absolute increases in lung V20 Gy, V5 Gy, and MLD of 3.3%, 5.0%, and 1.0 Gy, respectively.Nearly 40% of RT plans overall, and 73% when switched to IMRT, were predicted to have reductions in MHD4 Gy with potentially clinically acceptable tradeoffs in lung dose. These observations demonstrate that decision support software for optimizing heart-lung dosimetric tradeoffs is feasible and may identify patients who might benefit most from more advanced RT technologies.

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.

Purpose:\ud Low-dose whole lung radiotherapy (LDLR) has been proposed as a treatment for patients with acute respiratory distress syndrome associated with SARS-CoV-2 infection and clinical trials are underway. There is an urgent need for preclinical evidence to justify this approach and inform dose, scheduling and mechanisms of action.\ud \ud Materials and methods:\ud Female C57BL/6 mice were treated with intranasal bleomycin sulphate (7.5 or 11.25 units/kg, day 0), then exposed to whole lung radiation therapy (0.5, 1.0, 1.5 Gy or sham, day 3). Bodyweight was measured daily and lung tissue harvested for histology and flow cytometry on day 10. Computed tomography (CT) lung imaging was performed pre-radiation (day 3) and pre-endpoint (day 10).\ud \ud Results:\ud Bleomycin caused pneumonitis of variable severity which correlated with weight loss. LDLR at 1.0 Gy was associated with a significant increase in the proportion of mice recovering to 98% of initial bodyweight and a proportion of these mice exhibited less severe histopathological lung changes. Mice experiencing moderate initial weight loss were more likely to respond to LDLR than those experiencing severe initial weight loss. Additionally, LDLR (1.0 Gy) significantly reduced bleomycin-induced increases in interstitial macrophages, CD103+ dendritic cells and neutrophil-DC hybrids. Overall, bleomycin-treated mice exhibited significantly higher percentages of non-aerated lung in left than right lungs and LDLR (1.0 Gy) limited further reductions in aerated lung volume in right but not left lungs. LDLR at 0.5 and 1.5 Gy did not improve bodyweight, flow cytometric or radiological readouts of bleomycin-induced pneumonitis.\ud \ud Conclusions:\ud Our data support the concept that LDLR can ameliorate acute inflammatory lung injury, identify 1.0 Gy as the most effective dose and provide evidence that it is more effective in the context of moderate than severe pneumonitis. Mechanistically, LDLR at 1.0 Gy significantly suppressed bleomycin-induced accumulation of pulmonary interstitial macrophages, CD103+ dendritic cells and neutrophil-DC hybrids.

To test the hypothesis that dynamic conformal arc therapy (DCAT) in Monaco, compared with volumetric modulated arc therapy (VMAT), maintains plan quality with higher delivery efficiency for lung stereotactic body radiotherapy (SBRT) and to investigate dosimetric benefits of DCAT with active breath-hold (DCAT+ABH), compared with free-breathing (DCAT+FB) for varying tumor sizes and motions. Fifty DCAT plans were used for lung SBRT. Randomly selected 17 DCAT plans were evaluated with respect to the retrospectively generated volumetric modulated arc therapy (VMAT) plans. The maximum dose at 2 cm from planning target volume (PTV) in any direction (D2cm/Rx), the ratio of 50% prescription isodose volume to the PTV (R50%), conformity index (CI), the lung volume receiving ≥20 Gy (V20), and monitor unit (MU) were evaluated. A t-test was used to evaluate the difference of plan quality between DCAT and VMAT. Internal target volume (ITV)/integrated-gross target volume (GTV) attributed by intra-fraction motion and lung V20 were stratified for DCAT+ABH and DCAT+FB across varying GTVs. DCAT maintained plan quality (p = 0.154 for D2cm/Rx, p = 0.089 for R50%, p = 0.064 for CI, and p = 0.780 for lung V20) while reducing MUs up to 30% (p0.001) from 2748 MU (VMAT) to 1868 MU (DCAT). DCAT+ABH, compared to DCAT+FB, reduced tumor motion, resulting in 19% volume reduction of PTV and 60% reduction in lung V20, on average. The difference in lung V20 between DCAT+ABH and DCAT+FB increased as the target size increased. The DCAT is a favorable approach compared with VMAT. These results support the utility of DCAT as a routine planning platform for lung SBRT, especially when utilized with respiratory motion management using the ABH.

ZusammenfassungDie systemische Sklerose mit interstitieller Lungenerkrankung (SSc-ILD) ist mit einem erhöhten Morbiditäts- und Mortalitätsrisiko verknüpft. Da es an zugelassenen Medikamenten mangelt, die den Krankheitsverlauf einer SSc-ILD effektiv beeinflussen, besteht ein hoher Bedarf an neuen Therapieoptionen. Die Behandlung mit immunmodulierenden Therapien sowie der autologen Stammzelltransplantation wird in klinischen Studien aktuell weiter untersucht. Kürzlich belegte zudem eine Phase-III-Studie die positive Wirkung des antifibrotischen Wirkstoffs Nintedanib auf den Verlust an Lungenvolumen und somit die Krankheitsprogression bei Patienten mit SSc-ILD. Eine Kombinationstherapie aus Nintedanib und Mycophenolat könnte basierend auf synergistischen Wirkprinzipien zukünftig einen ergänzenden Behandlungsansatz der SSc-ILD darstellen.

Micro-computed tomography (micro-CT) imaging is an emerging technology with many applications in small animals, for example, the study of pulmonary diseases, although clear guidelines and critical mass of evidence are still missing in the preclinical literature. The neonatal rabbit is a valuable model for studying pulmonary development. However, the longitudinal monitoring of lung function by micro-CT can be challenging. Distinctive datasets corresponding to the end-inspiration and end-expiration phases need to be generated and analyzed to derive lung-functional parameters. The quality of CT scans and the reliability of parameters obtained remain highly dependent on the anesthesia protocol used. Three different anesthetic protocols were tested. The combination of dexmedetomidine 0.25 mg/kg injected intraperitoneally followed by 1% isoflurane was found to facilitate CT imaging at 4 and 11 days after birth. Contrarily, isoflurane and ketamine-xylazine were found unsuitable and thus not investigated further. Total lung volumes significantly increased at day 11 compared with baseline in both respiratory phases, whereas lung tissue remained constant. As expected, functional residual capacity, air-to-tissue ratio, and minute ventilation were significantly increased at day 11 in each animal. Those parameters were correlated with inspiratory capacity, compliance, elastance, and resistance of both respiratory system and tissue component, as measured by flexiVent. Lung development was also evaluated by histomorphometric analyses. In conclusion, we have identified a safe and suitable anesthesia protocol for micro-CT imaging in neonatal rabbits. Moreover, the possibility to longitudinally measure lung function in the same subject dramatically reduced the intraexperimental variability.

Background During exercise, dynamic hyperinflation (DH), measured by a reduction in inspiratory capacity (IC), increases exertional dyspnea and reduces functional capacity in many patients with severe COPD. Although noninvasive ventilation (NIV) during exercise can improve exercise duration, the effect on DH is unclear. Research Questions In people with COPD, resting hyperinflation, and evidence of DH during exercise, does bilevel NIV during exercise reduce DH and increase endurance time compared with exercise with no NIV, and does NIV with an individually titrated expiratory positive airway pressure (T-EPAP) reduce DH and increase exercise endurance time more than does NIV with standardized EPAP (S-EPAP) of 5 cm H2O? Study Design and Methods A randomized crossover trial in which investigators and participants were blinded between NIV interventions was performed. Participants (N = 19; FEV1 of 1.02 ± 0.24 L (39% ± 6% predicted) completed three constant work rate endurance cycle tests in random order—no NIV, NIV with S-EPAP, and NIV with T-EPAP—during exercise. Primary outcomes were isotime IC and exercise endurance time. Outcome measures from each intervention were compared at isotime and at end exercise by using a linear mixed-model analysis. Results Compared with those with no NIV, isotime IC and endurance time were greater with both NIV with S-EPAP (mean difference: 95% CI, 0.19 L [0.10-0.28]; 95% CI, 153 s [24-280], respectively) and T-EPAP (95% CI, 0.22 L [0.13-0.32]; 95% CI, 145 s [28-259], respectively). There was no difference between NIV with S-EPAP and NIV with T-EPAP. Interpretation In people with COPD and DH during exercise, NIV during exercise reduced DH and increased cycle endurance time. An S-EPAP of 5 cm H2O was adequate to obtain these benefits. Trial Registry Australian New Zealand Clinical Trials Registry; No.: ACTRN12613000804785; URL: http://www.anzctr.org.au

Pulmonary function testing (PFT) is an important component of the evaluation, monitoring, and management of patients with suspected or established lung disease. Spirometry is easily accomplished in the primary care office setting; determination of lung volumes and diffusion capacity is performed in a pulmonary laboratory. Spirometry evaluates vital capacity of the lungs and expiratory flow rates and provides both numeric data and a graphic depiction of respiratory air flow. Characteristic patterns in spirometry-derived data allow the clinician to identify potential lung disease, as well as establish relative reversibility of airflow abnormalities.

Objectives To assess the feasibility of magnetic resonance imaging (MRI) for postnatal assessment of pulmonary vascularity in infants with congenital diaphragmatic hernia (CDH). Study design Infants with prenatally diagnosed CDH (n = 24) received postnatal pulmonary MRI. Infants with nonpulmonary birth defects served as controls (n = 5). Semiautomatic segmentation was performed to obtain total vascular volume using time of flight images to assess vascularity. Results Average vascular density (vascular volume/lung volume) in control infants was 0.23 ± 0.06 mm3/mm3 compared with 0.18 ± 0.06 mm3/mm3 in infants with CDH is (P = .09). When stratified further based on CDH severity, the difference between control infants and moderate CDH group was statistically significant. (0.23 mm3/mm3 vs 0.15 mm3/mm3, P = .01). Ipsilateral vascular density on MRI in infants with CDH significantly correlated with the prenatal pulmonary hypertensive index (P = .0004, Spearman R = +0.87) and with number of days on mechanical ventilation (P = .04, Spearman R = −0.44), total days on inhaled nitric oxide (P = .02, Spearman R = −0.47), use of epoprostenol for acute pulmonary hypertension (PH) (0.14 mm3/mm3 vs 0.20 mm3/mm3, P = .005), and use of sildenafil for chronic PH (0.15 mm3/mm3 vs 0.19 mm3/mm3, P = .03). Conclusions Our results suggest that postnatal pulmonary vascularity assessed by MRI strongly correlates with prenatal and postnatal markers of PH severity and that pulmonary vascularity may serve as a direct measure of pulmonary vascular hypoplasia in infants with CDH.

Nano-particulate matters (NPM) induced the lung injury in mice were evaluated using quantitative micro-computed tomography in the present article. It is an important negative effect of health problems that NPM exposure provokes changes in the lung injury. The micro-computed tomography (CT) to assess lung injury in mouse models has been investigated. The dynamic structural changes in a NPM-induced lung injury mouse mode were monitored. Adults female BALB/C mice were repeatedly exposed to NPM, and micro-CT scans were performed at day 0, 3, 5 and 9. Lung samples were also collected for histological analysis at each time point. The total lung volume, the injured lung volume, and the normal lung volume were defined and calculated volume during the phase of NPM-exposure on the mice. The total and injured lung volumes of NPM-exposed mice were significantly larger than those of the mice at day 5 and 9. The data from micro-CT was consistent with alveolar enlargement and destruction by histological quantification from pathological section. The study for NPM-induced lung injury model by micro-CT may extend our understanding of the distinct pathophysiology of NPM induced lung injury in mice.

Introduction When performing computerized tomography chest imaging in children, obtaining high quality, motion-free images is important in the accurate diagnosis of underlying pathology. General anesthesia is associated with the development of atelectasis, which can impair accurate diagnosis by obscuring or altering the appearance of the lung parenchyma or airways. Recruitment maneuvers, performed by anesthesiologists, can be used to effectively re-expand atelectatic lung. Methods The computerized tomography chest imaging in 44 children aged between 2 months and 7 years, undergoing serial imaging for monitoring of cystic fibrosis, were reviewed and graded for atelectasis. The first scan performed on each child was performed with a supraglottic airway device and a non-standardized recruitment maneuver. The second scan on each child was performed with a cuffed endotracheal tube and a standardized recruitment maneuver. Results When a supraglottic airway device and a non-standardized recruitment maneuver were used, 77% of patients demonstrated atelectasis of any degree on their computerized tomography chest imaging, compared with only 39% when a cuffed endotracheal tube and standardized recruitment maneuver were used. The percentage of computerized tomography chest scans that were scored acceptable (with either a total combined lung atelectasis score of 0 or 1) improved from 37% to 75% when a cuffed endotracheal tube and standardized recruitment maneuver where used. In particular, the mean atelectasis score for both lungs improved from 2.91 (SD ± 2.6) to 1.11 (SD ± 1.9), with a mean difference of 1.8 (95% CI 0.82-2.77) (p 0.0004). Conclusion The use of a cuffed endotracheal tube and a standardized recruitment maneuver is an effective way to reduce atelectasis as a result of general anesthesia. Anesthesiologists can actively contribute towards improved image quality through their choice of airway and recruitment maneuver.

New findings What is the central question of this study? Does endogenous testosterone modulate the consequences of IH in the lungs of male mice ? What is the main finding and its importance? Orchiectomized mice exposed to IH develop a pattern that is similar to emphysema or obstructive lung disease with elevated lung volumes, low pulmonary elastance during a methacholine challenge test and high counts of lymphocytes in bronchoalveolar lavages. Since low testosterone levels and other respiratory diseases are common in sleep apnea there is a clear clinical relevance to these results. Abstract We tested the hypothesis that low testosterone levels modulate the pulmonary responses to intermittent hypoxia (IH - used as a model of sleep apnoea) in male mice. We used intact (SHAM) or orchiectomised (ORX) mice exposed to IH for 14 days (12h/day, 10cycles/h, 6% oxygen) or to normoxia (Nx). We first measured ventilation and metabolic rates in freely behaving mice (whole body plethysmography) and then respiratory mechanics in tracheotomised mice (flexiVent). We assessed the respiratory system resistance (Rrs) and elastance (Ers), Newtonian resistance (Rn: resistance of the large airways), tissue damping (G) and tissue elastance (H) under baseline conditions and during a methacholine challenge test. We also measured the quasi-static compliance (Cst) and inspiratory capacity with partial pressure-volume loops. Finally, inflammatory cells were counted in the broncho-alveolar lavage (BAL) and we measured lung volume by water displacement. ORX-IH mice had higher tidal volume, inspiratory capacity, and lung volume compared to the other groups, but showed signs of low efficiency of O2 exchange rate relative to minute ventilation. During the methacholine challenge, orchiectomy decreased the values of most mechanical parameters and IH reduced Ers and H leading to very low values in ORX-IH mice. Finally, the total number of cells and the number of lymphocytes in BAL were both increased by IH in ORX mice. Since reduced lung elasticity, low O2 extraction, increased lung volumes, and inflammation are signs of emphysematous lung disease, we conclude that testosterone might prevent lung emphysema during IH exposures. This article is protected by copyright. All rights reserved.

OBJECTIVES To identify drivers of time from diagnosis to treatment (TTT) of surgically resected early stage non-small cell lung cancer (NSCLC) and determine the effect of TTT on post-resection survival. SUMMARY BACKGROUND DATA Large database studies that lack relevant comorbidity data have identified longer TTT as a driver of worse overall survival. METHODS From 1/1/2014-4/1/2018, 599 patients underwent lung resection for clinical stage I and II NSCLC. Random forest classification, regression, and survival were used to estimate likelihood of TTT=0 (tissue diagnosis obtained at surgery), > 0 (diagnosis obtained pre-resection), and effect of TTT on all-cause mortality. RESULTS Patients with TTT > 0 (n=413) had median TTT of 42 days [25-75th percentile: 27-59 days]. Patients with TTT=0 (n=186) had smaller tumors and higher percent predicted forced expiratory volume in one second (FEV1%). Patients with history of stroke, oncology consultation, invasive mediastinal staging, low and high extremes of FEV1% had longer TTT. Higher clinical stage, lack of preoperative stress test, anemia, older age, lower FEV1% and diffusion lung capacity, larger tumor size, and longer TTT were the most important predictors of all-cause mortality. One- and five-year overall survival decreased when TTT was longer than 50 days. CONCLUSION Preoperative physiologic workup and multidisciplinary evaluation were the predominant drivers of longer TTT. Patients with TTT=0 have more favorable presentation and should be considered in TTT analyses for early stage lung cancer populations. The time needed to clinically stage and optimize patients for resection is not deleterious to overall survival until resection is performed after 50 days from diagnosis.

NEW FINDINGS: What is the central question of this study? Are chronotropic responses to a 6-minute walk test different in women with post-acute coronavirus disease 2019 (COVID-19) syndrome compared with control subjects? What is the main finding and its importance? Compared with control subjects, the increase in heart rate was attenuated and recovery delayed after a 6-minute walk test in participants after infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Women reporting specific symptoms at time of testing had greater impairments compared with control subjects and SARS-CoV-2 participants not actively experiencing these symptoms. Such alterations have potential to constrain not only exercise tolerance but also participation in free-living physical activity in women during post-acute recovery from COVID-19. ABSTRACT: The short-term cardiopulmonary manifestations of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are well defined. However, the implications of cardiopulmonary sequelae, persisting beyond acute illness, on physical function are largely unknown. Herein, we characterized heart rate responses to and recovery from a 6-minute walk test (6MWT) in women ∼3 months after mild-to-moderate SARS-CoV-2 infection compared with non-infected control subjects. Forty-five women (n = 29 SARS-CoV-2; n = 16 controls; age = 56 ± 11 years; body mass index = 25.8 ± 6.0 kg/m2 ) completed pulmonary function testing and a 6MWT. The SARS-CoV-2 participants demonstrated reduced total lung capacity (84 ± 8 vs. 93 ± 13%; P = 0.006), vital capacity (87 ± 10 vs. 93 ± 10%; P = 0.040), functional residual capacity (75 ± 16 vs. 88 ± 16%; P = 0.006) and residual volume (76 ± 18 vs. 93 ± 22%; P = 0.001) compared with control subjects. No between-group differences were observed in 6MWT distance (P = 0.194); however, the increase in heart rate with exertion was attenuated among SARS-CoV-2 participants compared with control subjects (+52 ± 20 vs. +65 ± 18 beats/min; P = 0.029). The decrease in heart rate was also delayed for minutes 1-5 of recovery among SARS-CoV-2 participants (all P

Introduction: Cardiovascular Diseases (CVD) are the main cause of morbidity and mortality in developed and developing countries. According to World Health Organization estimates, 17.9 million people died of CVD in 2016, representing 31% of all global deaths. Material and Method: Integrative review carried out in the databases PubMed, SciELO, Lilacs and PEDro, based on the guiding question of the search: “what is the effect of respiratory techniques on the lung function of patients undergoing cardiac surgery?”, And crossing of the terms: breathing exercises AND preoperative AND cardiac surgery (all terms present in MEsh and DeCs) from May to June 2020. Results: 104 articles were found in the selected databases, 67 articles were excluded, 37 were selected for full reading, eight of which were part of this review. Discussion: The present integrative review aimed to analyze the effects of respiratory techniques on lung function in patients undergoing cardiac surgery. Patients undergoing a cardiac surgical procedure, mainly develop postoperative pulmonary dysfunction with significant reduction in lung volumes, impaired respiratory function, decreased lung compliance and increased respiratory work. Final Considerations: Respiratory techniques such as breathing exercises and / or respiratory muscle training employed in patients undergoing a cardiac surgical procedure, improve lung function, consequently improving respiratory muscle strength as a whole, also interfering in the reduction of post-respiratory complications. CRM in this population.Keywords: Cardiac surgery; Breathing Exercises; Preoperative.

Radiation pneumonitis is a rare but possibly fatal side effect of Yttrium-90 (90Y) radioembolization. It may occur 1 to 6 months after therapy, in case a significant part of the 90Y microspheres shunt to the lungs. In current clinical practice, a predicted value of lung dose greater than 30Gy is considered a criterion to exclude patients from treatment. However, contrasting findings regarding the occurrence of radiation pneumonitis and lung dose were previously reported in literature. In this study, the relationship between the lung dose value and the eventual occurrence of radiation pneumonitis after 90Y radioembolization was investigated. Methods: A total of 317 90Y liver radioembolization procedures performed during an 8-years period (Feb.2012-Sep.2020) were retrospectively analyzed. Predicted lung mean dose using 99mTc-MAA planar scintigraphy (LMDMAA) acquired during the planning phase and left lung mean dose (LMDY-90) using the 90Y PET/CT acquired after the treatment were calculated. For the lung dose computation, it was chosen to use the left lung as representative lung volume, to compensate for the scatter from the liver moving in the cranial-caudal direction due to breathing and mainly affecting the right lung. Results: Two hundred and seventy-two patients underwent 90Y procedures, of which 63% performed with glass microspheres and 37% with resin microspheres. Median injected activity was 1974MBq (range: 242-9538MBq). Median LMDMAA was 3.5Gy (range: 0.2-89.0Gy). For 14 procedures LMDMAA was >30Gy. Median LMDY-90 was 1Gy (range: 0.0-22.1Gy). No patients had a LMDY-90 >30Gy. Of the three patients with a LMDY-90 >12Gy, two patients (LMDY-90 = 22.1Gy, LMDMAA = 89Gy and LMDY-90 = 17.7Gy, LMDMAA = 34.1Gy, respectively) developed radiation pneumonitis and consequently died. A third patient with a LMDY-90 equal to 18.4Gy (LMDMAA = 29.1Gy) died 2 months after treatment, before imaging evaluation, due to progressive disease. Conclusion: The occurrence of radiation pneumonitis as a consequence of lung shunt following 90Y radioembolization is rare (

Background Continuous positive airway pressure (CPAP) is a primary mode of respiratory support for preterm infants. Animal studies have shown long-term detrimental effects on lung/airway development, particularly airway (AW) hyper-reactivity, as an unfortunate consequence of neonatal CPAP. Since the hyaluronan (HA) synthesizing enzyme hyaluronan synthase-3 (HAS3) is involved in various adult pulmonary disorders, the present study used a neonatal mouse model to investigate the role of HAS3 in CPAP-induced AW hyper-reactivity. Methods Male and female neonatal mice were fitted with a custom-made mask for delivery of daily CPAP 3 h/day for 7 days. At postnatal day 21 (2 weeks after CPAP ended), airway (AW) hyper-reactivity and HAS3 expression were assessed with and without in vitro HAS3 siRNA treatment. Results MRIs of 3-day-old mice confirmed that CPAP increased lung volume with incrementing inflation pressures. CPAP increased AW reactivity in both male and female mice, which was associated with increased airway smooth muscle and epithelial HAS3 immunoreactivity. CPAP did not affect HA accumulation, but HAS3 siRNA reversed CPAP-induced AW hyper-reactivity and reduced HAS3 expression. Conclusions These data in mice implicate a role for HAS3 in long-term effects of CPAP in the developing airway in the context of preterm birth and CPAP therapy. Impact Neonatal CPAP increases airway smooth muscle and epithelial HAS3 expression in mice. CPAP-induced airway hyper-reactivity is modulated by HAS3. These data enhance our understanding of the role mechanical forces play on lung development. These data are a significance step toward understanding CPAP effects on developing airway. These data may impact clinical recognition of the ways that CPAP may contribute to wheezing disorders of former preterm infants.

Background The long-term post-acute pulmonary sequelae of COVID-19 remain unknown. Purpose To evaluate lung injury in patients affected by COVID-19 pneumonia at the 6-month follow-up CT examination compared with the baseline chest CT examination. Materials and Methods From March 19, 2020, to May 24, 2020, patients with moderate to severe COVID-19 pneumonia who had undergone baseline chest CT were prospectively enrolled at their 6-month follow-up. The CT qualitative findings, semiquantitative Lung Severity Score (LSS), and the well-aerated lung volume at quantitative chest CT (QCCT) analysis were analyzed. The performance of the baseline LSS and QCCT findings for predicting fibrosis-like changes (reticular pattern and/or honeycombing) at the 6-month follow-up chest CT examination was tested by using receiver operating characteristic curves. Univariable and multivariable logistic regression analyses were used to test clinical and radiologic features that were predictive of fibrosis-like changes. The multivariable analysis was performed with clinical parameters alone (clinical model), radiologic parameters alone (radiologic model), and the combination of clinical and radiologic parameters (combined model). Results One hundred eighteen patients who had undergone baseline chest CT and agreed to undergo follow-up chest CT at 6 months were included in the study (62 women; mean age, 65 years ± 12 [standard deviation]). At follow-up chest CT, 85 of 118 (72%) patients showed fibrosis-like changes and 49 of 118 (42%) showed ground-glass opacities. The baseline LSS (>14) and QCCT findings (≤3.75 L and ≤80%) showed excellent performance for predicting fibrosis-like changes at follow-up chest CT. In the multivariable analysis, the areas under the curve were 0.89 (95% CI: 0.77, 0.96) for the clinical model, 0.81 (95% CI: 0.68, 0.9) for the radiologic model, and 0.92 (95% CI: 0.81, 0.98) for the combined model. Conclusion At 6-month follow-up chest CT, 72% of patients showed late sequelae, in particular fibrosis-like changes. The baseline Lung Severity Score and the well-aerated lung volume at quantitative chest CT (QCCT) analysis showed excellent performance for predicting fibrosis-like changes at the 6-month chest CT (area under the curve, >0.88). Male sex, cough, lymphocytosis, and the well-aerated lung volume at QCCT analysis were significant predictors of fibrosis-like changes at 6 months, demonstrating an inverse correlation (area under the curve, 0.92). © RSNA, 2021 See also the editorial by Wells and Devaraj in this issue.

Background Maximal respiratory pressures (MRP) obtained at functional residual capacity (FRC) may reflect the real respiratory muscle pressure. Objectives To evaluate concurrent validity, test-retest, and inter-rater reliability of MRP performed with a new instrument in healthy individuals, and to compare values obtained at different volumes in healthy individuals and individuals with COPD. Methods MRP of 100 healthy individuals were obtained using the TrueForce and the MicroRPM® at residual volume (RV) and total lung capacity (TLC) to evaluate concurrent validity. MRP were obtained at FRC using the TrueForce to evaluate reliability. Comparisons of inspiratory pressure values (FRC compared to RV) and expiratory pressure values (FRC compared to TLC) were performed with 100 healthy individuals and 15 individuals with COPD. Results The intraclass correlation coefficient (ICC) was 0.77 and 0.86 for concurrent validity for inspiratory and expiratory pressures, respectively. Test-retest reliability showed an ICC of 0.87 for inspiratory pressure, and 0.78 for expiratory pressure; inter-rater reliability showed an ICC of 0.91 for inspiratory pressure, and 0.84 for expiratory pressure. Measurements performed at RV and TLC were higher when compared to FRC [mean difference (95%CI)= -8.30 (-11.82, -4.78) cmH2O; -37.29 (-42.63, -31.96) cmH2O] in healthy individuals, and -11.09 (-15.83, -6.35) cmH2O; -57.14 (-71.05, -43.05) cmH2O in COPD, for inspiratory and expiratory pressures, respectively. Conclusion MRP performed with the TrueForce presented good concurrent validity, good test-retest reliability, excellent inter-rater reliability for inspiratory pressure and good inter-rater reliability for expiratory pressure. MRP were lower when obtained at FRC for healthy individuals and with COPD.

BACKGROUND Donor-recipient size-matching has been repeatedly reported to improve outcomes following lung transplantation (LTx). However, there is significant variability in practice and the optimal strategy for size-matching is yet to be defined. For recipients with ILD, size-matching decisions are complicated by concerns regarding the potential impact of pre-LTx pulmonary restriction. We evaluate whether a specific donor-to-recipient size-matching strategy, based on predicted total lung capacity, benefits this patient group. METHODS This retrospective, single-centre, cohort study describes the post-LTx outcomes of adults who underwent LTx for ILD between 1983 and 2020. Only patients with restrictive physiology, based on pre-LTx pulmonary function testing were included. Post-LTx outcomes were compared based on donor-recipient predicted TLC (D-R pTLC) ratio. A D-R pTLC ratio of ≥0.8 or

Ex vivo lung perfusion (EVLP) has being increasingly used for the pretransplant assessment of extended-criteria donor lungs. Mathematical models to predict lung acceptance during EVLP have not been reported so far. Thus, we hypothesized that predictors of lung acceptance could be identified and used to develop a mathematical model describing the clinical decision-making process used in our institution. Donor lungs characteristics and EVLP physiologic parameters included in our EVLP registry were examined (derivation cohort). Multivariable logistic regression analysis was performed to identify predictors independently associated with lung acceptance. A mathematical model (EX vivo lung PerfusIon pREdiction [EXPIRE] model) for each hour of EVLP was developed and validated using a new cohort (validation cohort). Two hundred eighty donor lungs were assessed with EVLP. Of these, 186 (66%) were accepted for transplantation. ΔPO2 and static compliance/total lung capacity were identified as independent predictors of lung acceptance and their respective cut-off values were determined. The EXPIRE model showed a low discriminative power at the first hour of EVLP assessment (AUC: 0.69 [95% CI: 0.62-0.77]), which progressively improved up to the fourth hour (AUC: 0.87 [95% CI: 0.83-0.92]). In a validation cohort, the EXPIRE model demonstrated good discriminative power, peaking at the fourth hour (AUC: 0.85 [95% CI: 0.76-0.94]). The EXPIRE model may help to standardize lung assessment in centers using the Toronto EVLP technique and improve overall transplant rates.

Quantitative retrospective analysis of the normal lung irradiation due to the variations of the ITV volume based on the techniques used for upper lobe (UL), mid lobe (ML), and lower lobe (LL) lung tumours when used with 2-view, 1-view, 0-view based LOT technique on Cyberknife, AveIP on Helical Tomotherapy, and DIBH on VMAT systems. In the treatment of lung tumours, patients medically inoperable or those who are unwilling to undergo surgery have the option to be treated using radiation therapy. There are many motion control techniques available for the treatment of the moving target, such as movement encompassment, respiratory gating, breath-hold, motion reduction, and tumour monitoring. ITV generation is dependent on technique and hence the volume of the PTVs will differ based on the technique used. This study aimed to determine the influence of these ITVs on the irradiated normal lung volume for UL, ML, and LL lung tumours for 23 patients. The mean difference in the PTV volumes generated with the 0-view technique was significant with that of 2-view and DIBH techniques (p-value 0.11). In the treatment of lung tumour patients with SBRT, this study has demonstrated 2-view with Cyberknife and DIBH with VMAT treatment techniques have optimal normal lung tissue sparing. There was a significant increase in the average lung volume receiving 5%,10%, 20%, and 30% dose when comparing the 1-view, 0-view, AveIP, and DIBH techniques to the 2-view technique. However, DIBH with VMAT was dosimetrically advantageous for ML and LL tumours, while providing significantly shorter treatment times than any other technique studied.

Background/objective Endotracheal suction is one of the most common and harmful procuedres performed on mechanically ventilated children. The aim of the study was to establish the feasibility of a randomised controlled trial (RCT) examining the effectiveness of normal saline instillation (NSI) and a positive end-expiratory pressure recruitment manoeuvre (RM) with endotracheal suction in the paediatric intensive care unit. Methods Pilot 2 × 2 factorial RCT. The study was conducted at a 36-bed tertiary paediatric intensive care unit in Australia. Fifty-eight children aged less than 16 years undergoing tracheal intubation and invasive mechanical ventilation. (i) NSI or no NSI and (ii) RM or no RM with endotracheal suction . The primary outcome was feasibility; secondary outcomes were ventilator-associated pneumonia (VAP), change in end-expiratory lung volume assessed by electrical impedance tomography, dynamic compliance, and oxygen saturation-to-fraction of inspired oxygen (SpO2/FiO2) ratio. Results/Findings Recruitment, retention, and missing data feasibility criteria were achieved. Eligibility and protocol adherence criteria were not achieved, with 818 patients eligible and 58 enrolled; cardiac surgery was the primary reason for exclusion. Approximately 30% of patients had at least one episode of nonadherence. Children who received NSI had a reduced incidence of VAP; however, this did not reach statistical significance (incidence rate ratio = 0.12, 95% confidence interval = 0.01–1.10; p = 0.06). NSI was associated with a significantly reduced SpO2/FiO2 ratio up to 10 min after suction. RMs were not associated with a reduced VAP incidence (incidence rate ratio = 0.31, 95% confidence interval = 0.05–1.88), but did significantly improve end-expiratory lung volume at 2 and 5 min after suction, dynamic compliance, and SpO2/FiO2 ratio. Conclusion RMs provided short-term improvements in end-expiratory lung volume and oxygenation. NSI with suction led to a reduced incidence of VAP; however, a definitive RCT is needed to test statistical differences. A RCT of study interventions is worthwhile and may be feasible with protocol modifications including the widening of participant eligibility.

Background/aim To evaluate the incidence and grade of radiation pneumonitis after volumetric modulated arc therapy (VMAT) performed for the treatment of non-small cell cancer (NSCLC). Patients and methods Fifty consecutive non-surgical candidates with NSCLC underwent VMAT. Thirty-five patients had stage-III tumors and 15 had recurrent tumors. The prescribed radiation dose for the gross tumor and the elective nodal area was 69 Gy in 30 fractions and 51 Gy in 30 fractions, respectively. Results Radiation pneumonitis developed in 38 patients (76%, 38/50), and grade ≥2 radiation pneumonitis developed in 11 patients (22%, 11/50). The percentage of lung volume that received a dose in excess of 5 Gy (V5), V10, V20, V30, and the mean lung dose (MLD) in the bilateral and ipsilateral lung were significantly associated with the development of grade ≥2 radiation pneumonitis. Conclusion The incidence and degree of radiation pneumonitis are acceptable following treatment of NSCLC with VMAT.

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.

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 The full range of long‐term health consequences in intensive care unit (ICU) survivors with COVID‐19 is unclear. This study aims to investigate the role of ventilatory support for long‐term pulmonary impairment in critically ill patients and further to identify risk factors for prolonged radiological recovery. Methods A prospective observational study from a single general hospital, including all with COVID‐19 admitted to ICU between March and August 2020, investigating the association between ventilatory support and the extent of residual parenchymal changes on chest computed tomography (CT) scan and measurement of lung volumes at follow‐up comparing high‐flow nasal oxygen (HFNO) or non‐invasive ventilation (NIV) with invasive ventilation. A semi‐quantitative score (CT involvement score) based on lobar involvement and a total score for all five lobes was used to estimate residual parenchymal changes. The association was calculated with logistic regression and adjusted for age, sex, smoking, and severity of illness. Results Among the 187 eligible, 86 had a chest CT scan and 76 a pulmonary function test at the follow‐up with a median time of 6 months after ICU discharge. Residual lung changes were seen in 74%. The extent of pulmonary changes was similar regardless of ventilatory support, but patients with invasive ventilation had a lower total lung capacity 84% versus 92% of predicted (p

The end of the acute period of COVID-19 does not mean complete recovery. Observation of patients in the post-COVID-19 period showed that a significant number of people experience shortness of breath, fatigue, muscle weakness, sleep disorders, cough, palpitations, so the term post-COVID-19 syndrome was coined. The examination to identify the causes of complaints of COVID-19 convalescents should include lung function assessment.The aim of the study was to assess the dynamics of lung function 4 months after hospitalization for COVID-19.Methods. 31 patients (26 males, the median age was 49 years) underwent traditional pulmonary function tests (PFTs) (spirometry, body plethysmography, test of diffusing lung capacity) and impulse oscillometry (IOS). Results. During the 1st visit, the average PFTs and IOS parameters were within the normal range in the whole group, apart from the diffusing lung capacity (DLCO), which was reduced mildly (on the border with moderate) in 77% of patients. During the 2nd visit, which was conducted on average 102 days after the 1st one, 58% of patients demonstrated abnormal lung diffusion capacity. The second assessment revealed a statistically significant increase in the slow and forced vital capacity (VC and FVC), the forced exhalation volume in 1 second (FEV1), total lung capacity (TLC), DLCO, and a decrease in the ratio of FEV1/FVC and the residual lung volume to TLC ratio.Conclusion. Post-COVID-19 patients show a statistically significant improvement of their lung function 4 months after hospital discharge. A systematic follow-up is essential for such patients to detect lung function abnormalities and correct them.

Background Radiation pneumonitis (RP) and radiation fibrosis (RF) are common side effects after breast cancer (BC) radiotherapy (RT). However, there is a great variation in the frequency of RP and RF. This study presents the occurrence of- and the treatment-related predictors for RP and RF. Further, physician- and patient-reported pulmonary symptoms during the first year after postoperative RT for BC are demonstrated. Materials and methods From 2007 to 2008, 250 BC patients referred for postoperative RT were included in a prospective cohort study and followed during the first year after RT. High-resolution computed tomography of the lungs and symptom registration were performed before RT and 3, 6, and 12 months after RT. Patient-reported symptoms were registered by standard quality of life questionnaires. Logistic regression analyses were applied to estimate treatment-related predictors for radiological RP (rRP), clinical RP (cRP), radiological RF (rRF), and clinical RF (cRF). Results The occurrence of rRP and cRP at three months was 78% and 19%, while 12 months after RT rRF and cRF was 89% and 16%, respectively; all reported as grade 1. In multivariable analyses, mastectomy predicted cRP at three months (OR = 2.48, p = .03) and cRF at six months, ipsilateral lung volume receiving 20 Gray or more (V20), V30, and mean lung dose (MLD) predicted rRP at six months (OR = 1.06, p = .0003; OR = 1.10, p = .001; and OR = 1.03, p = .01, respectively). Endocrine treatment predicted cRF at 12 months (OR = 2.48, p = .02). Physicians reported significant more dyspnea at 3 months (p = .003) and patients reported 'a little dyspnea' more at 3 and 12 months compared to baseline (p = .007). Conclusion RP and RF are prevalent in the first year after BC radiation. Mastectomy predicted cRP at three months. V20, V30, D25, and MLD predicted rRP at 6 months, and endocrine treatment predicted cRF at 12 months. Patients and physicians reported dyspnea differently.

BACKGROUND: Mechanical ventilation immediately after lung transplantation may impact the development of primary graft dysfunction (PGD), particularly in cases of donor-recipient size mismatch as ventilation is typically based on recipient rather than donor size. METHODS: We conducted a retrospective cohort study of adult bilateral lung transplant recipients at our center between January 2010 and January 2017. We defined donor-based lung protective ventilation (dLPV) as 6 to 8 ml/kg of donor ideal body weight and plateau pressure

Lung volume reduction surgery is a well-established treatment for pulmonary emphysema; however, lobectomy is performed infrequently in this indication. In a 48-year-old woman with chronic obstructive pulmonary disease at stage Global Initiative for Chronic Obstructive Lung Disease stage 3C, with previous lower bilobectomy due to severe poststenotic pneumonia and multiple ineffective endobronchial-valves placements, lower-lobe lobectomy as lung volume reduction surgery was performed through anterolateral thoracotomy. Forced expiratory volume in 1 second increased from 0.9l (31%) preoperative to 1.74l (59%) postoperatively. This case demonstrates that in well-selected patients, lobar resection for emphysema is feasible with good functional outcome even in patients after previous contralateral anatomic resection.

Purpose To investigate the sensitivity of Monte Carlo (MC) calculated lung dose distributions to lung tissue characterization in external beam radiotherapy of breast cancer under Deep Inspiration Breath Hold (DIBH). Methods EGSnrc based MC software was employed. Mean lung densities for one hundred patients were analysed. CT number frequency and clinical dose distributions were calculated for 15 patients with mean lung density below 0.14 g/cm3. Lung volume with a pre-defined CT numbers was also considered. Lung tissue was characterized by applying different CT calibrations in the low-density region and air-lung tissue thresholds. Dose impact was estimated by Dose Volume Histogram (DVH) parameters. Results Mean lung densities below 0.14 g/cm3 were found in 10% of the patients. CT numbers below −960 HU dominated the CT frequency distributions with a high rate of CT numbers at −990 HU. Mass density conversion approach influenced the DVH shape. V4Gy and V8Gy varied by 7% and 5% for the selected patients and by 9% and 3.5% for the pre-defined lung volume. V16Gy and V20Gy, were within 2.5%. Regions above 20 Gy were affected. Variations in air- lung tissue differentiation resulted in DVH parameters within 1%. Threshold at −990 HU was confirmed by the CT number frequency distributions. Conclusions Lung dose distributions were more sensitive to variations in the CT calibration curve below lung (inhale) density than to air-lung tissue differentiation. Low dose regions were mostly affected. The dosimetry effects were found to be potentially important to 10% of the patients treated under DIBH.

Introduction/aims In this study, researchers evaluated the effects of lung volume recruitment treatment (LVR) - a low-tech, low-cost, manual 'breath stacking' technique used to help people cough with enough force to clear their airways, thereby reducing the risk of aspiration and choking - on five volitional airway clearance and protection behaviors used by people living with amyotrophic lateral sclerosis (PwALS). Methods Using a repeated-measures cross-over design, 29 PwALS performed five volitional airway clearance and protection behaviors in LVR treatment and in no-treatment, control conditions. Peak cough flow (PCF) was used to measure maximum expiratory rate during forced expiration, throat clearing, hawking, post-swallow coughing and the supraglottic swallowing maneuver. Comparisons were made as a function of condition (treatment or control) and three time-points (pre-treatment, and 15- and 30-minutes post-treatment). Results LVR treatment had a significant positive effect on maximum expiratory rates during all tested airway clearance and protection behaviors. Increased PCF values lasted for up to 30 minutes post-LVR for all tested behaviors in the treatment condition. Discussion Findings demonstrate that LVR treatment can increase control over airway clearance in PwALS, as well as provide improved airway protection for up to 30 minutes, the duration of a typical meal. This study has implications for patient care. These include offering patients control over some of the most feared symptoms of ALS, particularly choking during activities of daily living, and enhanced ALS respiratory care in low-resource settings. Findings may have implications for other neurodegenerative disorders in which dysphagia occurs with retained sensory function. This article is protected by copyright. All rights reserved.

Objective To quantitatively evaluate computed tomography (CT) parameters of coronavirus disease 2019 (COVID-19) pneumonia an artificial intelligence (AI)-based software in different clinical severity groups during the disease course. Methods From March 11 to April 15, 2020, 51 patients (age, 18-84 years; 28 men) diagnosed and hospitalized with COVID-19 pneumonia with a total of 116 CT scans were enrolled in the study. Patients were divided into mild (n = 12), moderate (n = 31), and severe (n = 8) groups based on clinical severity. An AI-based quantitative CT analysis, including lung volume, opacity score, opacity volume, percentage of opacity, and mean lung density, was performed in initial and follow-up CTs obtained at different time points. Receiver operating characteristic analysis was performed to find the diagnostic ability of quantitative CT parameters for discriminating severe from nonsevere pneumonia. Results In baseline assessment, the severe group had significantly higher opacity score, opacity volume, higher percentage of opacity, and higher mean lung density than the moderate group (all P ≤ 0.001). Through consecutive time points, the severe group had a significant decrease in lung volume (P = 0.006), a significant increase in total opacity score (P = 0.003), and percentage of opacity (P = 0.007). A significant increase in total opacity score was also observed for the mild group (P = 0.011). Residual opacities were observed in all groups. The involvement of more than 4 lobes (sensitivity, 100%; specificity, 65.26%), total opacity score greater than 4 (sensitivity, 100%; specificity, 64.21), total opacity volume greater than 337.4 mL (sensitivity, 80.95%; specificity, 84.21%), percentage of opacity greater than 11% (sensitivity, 80.95%; specificity, 88.42%), total high opacity volume greater than 10.5 mL (sensitivity, 95.24%; specificity, 66.32%), percentage of high opacity greater than 0.8% (sensitivity, 85.71%; specificity, 80.00%) and mean lung density HU greater than -705 HU (sensitivity, 57.14%; specificity, 90.53%) were related to severe pneumonia. Conclusions An AI-based quantitative CT analysis is an objective tool in demonstrating disease severity and can also assist the clinician in follow-up by providing information about the disease course and prognosis according to different clinical severity groups.

Purpose Chronic obstructive pulmonary disease (COPD) limits respiration, which may negatively impact airway safety during swallowing. It is unknown how differences in lung volume in COPD may alter swallowing physiology. This exploratory study aimed to determine how changes in lung volume impact swallow duration and coordination in persons with stable state COPD compared with older healthy volunteers (OHVs). Method Volunteers ≥ 45 years with COPD (VwCOPDs; n = 9) and OHVs ( n = 10) were prospectively recruited. Group and within-participant differences were examined when swallowing at different respiratory volumes: resting expiratory level (REL), tidal volume (TV), and total lung capacity (TLC). Participants swallowed self-administered 20-ml water boluses by medicine cup. Noncued (NC) water swallows were followed by randomly ordered block swallowing trials at three lung volumes. Estimated lung volume (ELV) and respiratory–swallow patterning were quantified using spirometry and respiratory inductive plethysmography. Manometry measured pharyngeal swallow duration from onset of base of tongue pressure increase to offset of negative pressure in the pharyngoesophageal segment. Results During NC swallows, the VwCOPDs swallowed at lower lung volumes than OHVs ( p = .011) and VwCOPDs tended to inspire after swallows more often than OHVs. Pharyngeal swallow duration did not differ between groups; however, swallow duration significantly decreased as the ELV increased in VwCOPDs ( p = .003). During ELV manipulation, the COPD group inspired after swallowing more frequently at REL than at TLC ( p = .001) and at TV ( p = .002). In conclusion, increasing respiratory lung volume in COPD should improve safety by reducing the frequency of inspiration after a swallow.

To assess the relationship between the mechanical properties of the respiratory system, characterized by the constant phase model (CPM) parameters Rn, G, and H, and morphological measurements of 18-week-old male BALB/c mice (n= 31): body mass, nose-to-anus-length (NAL), and ex vivo lung volume. A small animal ventilator (SAV), an animal model of lung inflammation (OVA), and a control group (Control) underwent two different protocols of respiratory mechanics assessment under basal conditions: bolus (B) and continuous infusion (CI), which distinguished the type of phosphate-buffered saline (PBS) injection used during the procedure. Thus, four groups were assessed: OVA-B (n = 6), Control-B (n = 7), OVA-CI (n= 8), and Control-CI (n = 10). There were not any significant associations between ex vivo lung volume and the CPM parameters, in contrast to reported works when the volume of air trapped in the lungs is used instead of the whole organ volume. Significant negative correlations (p < 0.05) were found in the Control-CI group for the CPM parameters G and H with body mass (r= − 0.901 and r= − 0.759, respectively) and NAL (r= − 0.860 and r= − 0.861, respectively). In addition, differences in the η ( $\frac {G}{H}$ ) parameter between the groups Control-CI and OVA-B (p = 0.020), and in the ex vivo lung volumes between Control-B and OVA-B (p = 0.031) were also observed. The correlational analyses were deemed inconclusive in our overall study, despite some significant results, due to confounding results across the groups.

BACKGROUND Persistent tachypnea of infancy (PTI) is the most common interstitial lung disease in young children. As no standardized therapeutic guidelines exist, different pharmaceuticals are used to treat PTI; inhaled corticosteroids (ICS) and bronchodilators being mostly used. This observation assessed the effectiveness of bronchodilators and ICS in children with PTI enrolled in the children's interstitial lung diseases (chILD)-EU Register. METHODS Symptomatic children with PTI were observed according to a predetermined stepwise protocol including bronchodilators as the first choice treatment (6 weeks). In patients with incomplete response, additionally, ICS was given (12 weeks). Signs, symptoms, and pulmonary function were evaluated at three time points: at baseline, 6 (±1) weeks after initiation of bronchodilators, and 12 (±1) weeks after bronchodilators/ICS. RESULTS Thirty-one children (median age: 44 months, interquartile range [IQR]: 15-67) were included. The therapy was associated with a significant reduction of tachypnea (53.3% of patients, p = 0.02), exercise intolerance (52.2% of patients, p

In congenital diaphragmatic hernia (CDH), ultrasound (U/S) measurements of the contralateral lung commonly provide the observed-to-expected lung-to-head ratio (O/E LHR) and are used to determine the severity of pulmonary hypoplasia. Fetal magnetic resonance imaging (MRI) measurement of the observed-to-expected total lung volume (O/E TLV) has been used as an adjunct to O/E LHR in predicting outcomes. Since O/E LHR only measures the contralateral lung, we sought to investigate if MRI measurements of the contralateral lung volume (O/E CLV) can accurately predict outcomes in CDH. We hypothesize that O/E CLV is a better predictor of CDH outcomes than O/E LHR. We identified all infants with a prenatal diagnosis of CDH at our fetal center who had both MRI and U/S measurements. Using lung volume ratios of right–left 55:45, we calculated O/E CLV from O/E TLV. We used receiver-operating characteristic (ROC) curves to calculate the area under the curve (AUC) to compare the predictive accuracy of O/E CLV to O/E LHR for ECMO support, as well as survival to both discharge and 1 year. Seventy-four patients had complete prenatal imaging with 39% requiring ECMO support. The median O/E CLV was 48.0% and the median O/E LHR was 42.3%. O/E CLV was a better predictor of the need for ECMO support (AUC 0.81 vs. 0.74). O/E CLV was a better predictor of survival to discharge (AUC 0.84 vs. 0.64) and 1-year survival (AUC 0.83 vs. 0.63) than O/E LHR. O/E LHR is a well-validated standard for predicting outcomes and guiding prenatal counseling in CDH. We provide evidence that fetal MRI measurements of the contralateral lung volume corrected for gestational age were more accurate in predicting the need for ECMO and survival. Future prospective studies validating O/E CLV regarding outcomes and ECMO utilization are warranted. Level III, retrospective comparative study.

Limited data exist with regard to the outcome of the Nuss procedure for pectus excavatum repair in adults. Here, we analysed changes in lung capacity and thoracic morphology based on computed tomography (CT) imaging in adults with pectus excavatum before surgery, during bar insertion and after bar removal. Patients who underwent the Nuss procedure for pectus excavatum after the age of 20 were included in this study. Chest CT scans of the included participants were taken before the Nuss procedure, immediately before removal of the pectus bar and 6 months after removal of the pectus bar. Lung capacity and thoracic morphology measurements were made from the CT scans. Six patients aged 24-43 years were included in this study. After the Nuss procedure, lung capacity was decreased in all patients. Although the pectus bar was removed, lung capacity had not significantly increased and was almost the same volume as before the Nuss procedure. After the Nuss procedure, the funnel chest shape had improved in all cases, patients' thoracic spine had also moved forward as the thorax moved forward and patients' stoop had improved. Despite a lack of change in lung capacity, surgical modification should be considered to reduce stress on the thoracic spine and in turn, reduce pain in patients with pectus excavatum. However, further long-term observation seems necessary.

BACKGROUND: The Global Initiative for Obstructive Lung Disease (GOLD) does not promote diffusing capacity for carbon monoxide (DLCO) values in the evaluation of COPD. In GOLD spirometric stage I COPD patients, the clinical and prognostic impact of a low DLCO has not been explored. RESEARCH QUESTION: Could a DLCO threshold help define an increased risk of death and a different clinical presentation in these patients? STUDY DESIGN AND METHODS: GOLD stage I COPD patients (n = 360) were enrolled and followed over 109 +/- 50 months. Age, sex, pack-years' history, BMI, dyspnea, lung function measurements, exercise capacity, BODE index, and history of exacerbations were recorded. A cutoff value for DLCO was identified for all-cause mortality and the clinical and physiological characteristics of patients above and below the threshold compared. Cox regression analysis explored the predictive power of that cutoff value for all-cause mortality. RESULTS: A DLCO cutoff value of = 60%: 9% vs DLCO < 60%: 23%, P = .01). At a same FEV1% predicted and Charlson score, patients with DLCO < 60% had lower BMI, more dyspnea, lower inspiratory capacity (IC)/total lung capacity (TLC) ratio, lower 6-min walk distance (6MWD), and higher BODE. Cox multiple regression analysis confirmed that after adjusting for age, sex, pack-years history, smoking status, and BMI, a DLCO < 60% is associated with all-cause mortality (hazard ratio [HR], 95% CI = 3.37, 1.35-8.39; P = .009) INTERPRETATION: In GOLD I COPD patients, a DLCO < 60% predicted is associated with increased risk of death and worse clinical presentation. What the cause(s) of this association are and whether they can be treated need to be determined.

BACKGROUND: Smokers manifest varied phenotypes of pulmonary impairment. RESEARCH QUESTION: Which pulmonary phenotypes are associated with coronary artery disease (CAD) in smokers? STUDY DESIGN AND METHODS: We analyzed data from the University of Pittsburgh COPD Specialized Center for Clinically Oriented Research (SCCOR) cohort (n = 481) and the Genetic Epidemiology of COPD (COPDGene) cohort (n = 2,580). Participants were current and former smokers with > 10 pack-years of tobacco exposure. Data from the two cohorts were analyzed separately because of methodologic differences. Lung hyperinflation was assessed by plethysmography in the SCCOR cohort and by inspiratory and expiratory CT scan lung volumes in the COPDGene cohort. Subclinical CAD was assessed as the coronary artery calcium score, whereas clinical CAD was defined as a self-reported history of CAD or myocardial infarction (MI). Analyses were performed in all smokers and then repeated in those with airflow obstruction (FEV(1) to FVC ratio, < 0.70). RESULTS: Pulmonary phenotypes, including airflow limitation, emphysema, lung hyperinflation, diffusion capacity, and radiographic measures of airway remodeling, showed weak to moderate correlations (r < 0.7) with each other. In multivariate models adjusted for pulmonary phenotypes and CAD risk factors, lung hyperinflation was the only phenotype associated with calcium score, history of clinical CAD, or history of MI (per 0.2 higher expiratory and inspiratory CT scan lung volume; coronary calcium: OR, 1.2; 95% CI, 1.1-1.5; P = .02; clinical CAD: OR, 1.6; 95% CI, 1.1-2.3; P = .01; and MI in COPDGene: OR, 1.7; 95% CI, 1.0-2.8; P = .05). FEV(1) and emphysema were associated with increased risk of CAD (P < .05) in models adjusted for CAD risk factors; however, these associations were attenuated on adjusting for lung hyperinflation. Results were the same in those with airflow obstruction and were present in both cohorts. INTERPRETATION: Lung hyperinflation is associated strongly with clinical and subclinical CAD in smokers, including those with airflow obstruction. After lung hyperinflation was accounted for, FEV(1) and emphysema no longer were associated with CAD. Subsequent studies should consider measuring lung hyperinflation and examining its mechanistic role in CAD in current and former smokers.