Acquired tracheomalacia due to SARS-CoV-2 pneumonia.

INTRODUCTION: Several studies mentioned parenchymal findings after SARS-CoV-2 pneumonia, but few studies have mentioned alterations in the airways. The aim of this study was to estimate the prevalence of tracheomalacia and to analyse the clinical characteristics in a cohort of patients with SARS-CoV-2. METHODS: The study population consisted of all patients with SARS-CoV-2 admitted a hospital serving a population of 500 000 inhabitants. Patients were visited between 2 and 6 months after hospital discharge. In this visit, all patients were subjected to an exhaustive clinical questionnaire and underwent clinical examination, pulmonary function tests and chest CT. RESULTS: From February 2020 to August 2021, 1920 patients were included in the cohort and tracheomalacia was observed in 15 (0.8%) on expiratory HRCT imaging. All patients with tracheomalacia also presented ground glass opacities in the CT scan and 12 patients had airway sequelae. CONCLUSIONS: Tracheomalacia is an exceptional sequela of SARS-CoV-2 survivors.

The contribution of estimated dead space fraction to mortality prediction in patients with chronic obstructive pulmonary disease-a new proposal.

Background: Mortality due to chronic obstructive pulmonary disease (COPD) is increasing. However, dead space fractions at rest (VD/VTrest) and peak exercise (VD/VTpeak) and variables affecting survival have not been evaluated. This study aimed to investigate these issues. Methods: This retrospective observational cohort study was conducted from 2010-2020. Patients with COPD who smoked, met the Global Initiatives for Chronic Lung Diseases (GOLD) criteria, had available demographic, complete lung function test (CLFT), medication, acute exacerbation of COPD (AECOPD), Charlson Comorbidity Index, and survival data were enrolled. VD/VTrest and VD/VTpeak were estimated (estVD/VTrest and estVD/VTpeak). Univariate and multivariable Cox regression with stepwise variable selection were performed to estimate hazard ratios of all-cause mortality. Results: Overall, 14,910 patients with COPD were obtained from the hospital database, and 456 were analyzed after excluding those without CLFT or meeting the lung function criteria during the follow-up period (median (IQR) 597 (331-934.5) days). Of the 456 subjects, 81% had GOLD stages 2 and 3, highly elevated dead space fractions, mild air-trapping and diffusion impairment. The hospitalized AECOPD rate was 0.60 ± 2.84/person/year. Forty-eight subjects (10.5%) died, including 30 with advanced cancer. The incidence density of death was 6.03 per 100 person-years. The crude risk factors for mortality were elevated estVD/VTrest, estVD/VTpeak, ≥2 hospitalizations for AECOPD, advanced age, body mass index (BMI) <18.5 kg/m2, and cancer (hazard ratios (95% C.I.) from 1.03 [1.00-1.06] to 5.45 [3.04-9.79]). The protective factors were high peak expiratory flow%, adjusted diffusing capacity%, alveolar volume%, and BMI 24-26.9 kg/m2. In stepwise Cox regression analysis, after adjusting for all selected factors except cancer, estVD/VTrest and BMI <18.5 kg/m2 were risk factors, whereas BMI 24-26.9 kg/m2 was protective. Cancer was the main cause of all-cause mortality in this study; however, estVD/VTrest and BMI were independent prognostic factors for COPD after excluding cancer. Conclusions: The predictive formula for dead space fraction enables the estimation of VD/VTrest, and the mortality probability formula facilitates the estimation of COPD mortality. However, the clinical implications should be approached with caution until these formulas have been validated.

FEV1Q: a race-neutral approach to assessing lung function.

BACKGROUND: Forced expiratory volume in 1 s quotient (FEV1Q) is a simple approach to spirometry interpretation that compares measured lung function to a lower boundary. This study evaluated how well FEV1Q predicts survival compared with current interpretation methods and whether race impacts FEV1Q. METHODS: White and Black adults with complete spirometry and mortality data from the National Health and Nutrition Examination Survey (NHANES) III and the United Network for Organ Sharing (UNOS) database for lung transplant referrals were included. FEV1Q was calculated as FEV1 divided by 0.4 L for females or 0.5 L for males. Cumulative distributions of FEV1 were compared across races. Cox proportional hazards models tested mortality risk from FEV1Q adjusting for age, sex, height, smoking, income and among UNOS individuals, referral diagnosis. Harrell's C-statistics were compared between absolute FEV1, FEV1Q, FEV1/height2, FEV1 z-scores and FEV1 % predicted. Analyses were stratified by race. RESULTS: Among 7182 individuals from NHANES III and 7149 from UNOS, 1907 (27%) and 991 (14%), respectively, were Black. The lower boundary FEV1 values did not differ between Black and White individuals in either population (FEV1 first percentile difference ≤0.01 L; p>0.05). Decreasing FEV1Q was associated with increasing hazard ratio (HR) for mortality (NHANES III HR 1.33 (95% CI 1.28-1.39) and UNOS HR 1.18 (95% CI 1.12-1.23)). The associations were not confounded nor modified by race. Discriminative power was highest for FEV1Q compared with alternative FEV1 approaches in both Black and White individuals. CONCLUSIONS: FEV1Q is an intuitive and simple race-neutral approach to interpreting FEV1 that predicts survival better than current alternative methods.

Symptomatic post COVID patients have impaired alveolar capillary membrane function and high VE/VCO2.

BACKGROUND: Post COVID-19 syndrome is characterized by several cardiorespiratory symptoms but the origin of patients' reported symptomatology is still unclear. METHODS: Consecutive post COVID-19 patients were included. Patients underwent full clinical evaluation, symptoms dedicated questionnaires, blood tests, echocardiography, thoracic computer tomography (CT), spirometry including alveolar capillary membrane diffusion (DM) and capillary volume (Vcap) assessment by combined carbon dioxide and nitric oxide lung diffusion (DLCO/DLNO) and cardiopulmonary exercise test. We measured surfactant derive protein B (immature form) as blood marker of alveolar cell function. RESULTS: We evaluated 204 consecutive post COVID-19 patients (56.5 ± 14.5 years, 89 females) 171 ± 85 days after the end of acute COVID-19 infection. We measured: forced expiratory volume (FEV1) 99 ± 17%pred, FVC 99 ± 17%pred, DLCO 82 ± 19%, DM 47.6 ± 14.8 mL/min/mmHg, Vcap 59 ± 17 mL, residual parenchymal damage at CT 7.2 ± 3.2% of lung tissue, peakVO2 84 ± 18%pred, VE/VCO2 slope 112 [102-123]%pred. Major reported symptoms were: dyspnea 45% of cases, tiredness 60% and fatigability 77%. Low FEV1, Vcap and high VE/VCO2 slope were associated with persistence of dyspnea. Tiredness was associated with high VE/VCO2 slope and low PeakVO2 and FEV1 while fatigability with high VE/VCO2 slope. SPB was fivefold higher in post COVID-19 than in normal subjects, but not associated to any of the referred symptoms. SPB was negatively associated to Vcap. CONCLUSIONS: In patients with post COVID-19, cardiorespiratory symptoms are linked to VE/VCO2 slope. In these patients the alveolar cells are dysregulated as shown by the very high SPB. The Vcap is low likely due to post COVID-19 pulmonary endothelial/vasculature damage but DLCO is only minimally impaired being DM preserved.

Risk factors associated with severe adverse events in patients with relapsing polychondritis undergoing flexible bronchoscopy.

BACKGROUND: Patients with relapsing polychondritis (RP) sometimes experience upper airway collapse or lower airway stenosis, and bronchoscopy may provide a valuable typical image to confirm the diagnosis. This study aimed to identify potential risk factors associated with severe adverse effects during bronchoscopy. METHODS: We performed a retrospective cohort study of 82 consecutive patients with RP hospitalized at Peking Union Medical College Hospital between January 1, 2012 and December 31, 2022. Clinical features and disease patterns were compared among patients with RP undergoing bronchoscopy with or without severe adverse effects. Binary logistic regression analysis was performed to identify the associated risk factors. RESULTS: For patients with RP undergoing bronchoscopy with severe adverse effects, the forced vital capacity (FVC), forced vital capacity percent predicted values (FVC%), and peak expiratory flow were significantly lower (P = 0.001, P = 0.001, and P = 0.021, respectively) than those in the non-severe adverse effect subgroup. Binary logistic regression analysis revealed that low FVC% (odds ratio, 0.930; 95% confidence interval, 0.880-0.982; P = 0.009) was an independent risk factor for severe adverse events in patients undergoing bronchoscopy. CONCLUSIONS: Low FVC or FVC% suggests a high risk of severe adverse effects in patients with RP undergoing bronchoscopy. Patients with such risk factors should be carefully evaluated before bronchoscopy and adequately prepared for emergency tracheal intubation or tracheostomy.

Large airway T cells in adults with former bronchopulmonary dysplasia.

BACKGROUND: Bronchopulmonary Dysplasia (BPD) in infants born prematurely is a risk factor for chronic airway obstruction later in life. The distribution of T cell subtypes in the large airways is largely unknown. OBJECTIVE: To characterize cellular and T cell profiles in the large airways of young adults with a history of BPD. METHODS: Forty-three young adults born prematurely (preterm (n = 20), BPD (n = 23)) and 45 full-term-born (asthma (n = 23), healthy (n = 22)) underwent lung function measurements, and bronchoscopy with large airway bronchial wash (BW). T-cells subsets in BW were analyzed by immunocytochemistry. RESULTS: The proportions of both lymphocytes and CD8 + T cells in BW were significantly higher in BPD (median, 6.6%, and 78.0%) when compared with asthma (3.4% and 67.8%, p = 0.002 and p = 0.040) and healthy (3.8% and 40%, p < 0.001 and p < 0.001). In all adults born prematurely (preterm and BPD), lymphocyte proportion correlated negatively with forced vital capacity (r= -0.324, p = 0.036) and CD8 + T cells correlated with forced expiratory volume in one second, FEV1 (r=-0.448, p = 0.048). Correlation-based network analysis revealed that lung function cluster and BPD-birth cluster were associated with lymphocytes and/or CD4 + and CD8 + T cells. Multivariate regression analysis showed that lymphocyte proportions and BPD severity qualified as independent factors associated with FEV1. CONCLUSIONS: The increased cytotoxic T cells in the large airways in young adults with former BPD, suggest a similar T-cell subset pattern as in the small airways, resembling features of COPD. Our findings strengthen the hypothesis that mechanisms involving adaptive and innate immune responses are involved in the development of airway disease due to preterm birth.

Disease diagnosis and severity classification in pulmonary fibrosis using carbonyl volatile organic compounds in exhaled breath.

BACKGROUND: Pathophysiological conditions underlying pulmonary fibrosis remain poorly understood. Exhaled breath volatile organic compounds (VOCs) have shown promise for lung disease diagnosis and classification. In particular, carbonyls are a byproduct of oxidative stress, associated with fibrosis in the lungs. To explore the potential of exhaled carbonyl VOCs to reflect underlying pathophysiological conditions in pulmonary fibrosis, this proof-of-concept study tested the hypothesis that volatile and low abundance carbonyl compounds could be linked to diagnosis and associated disease severity. METHODS: Exhaled breath samples were collected from outpatients with a diagnosis of Idiopathic Pulmonary Fibrosis (IPF) or Connective Tissue related Interstitial Lung Disease (CTD-ILD) with stable lung function for 3 months before enrollment, as measured by pulmonary function testing (PFT) DLCO (%), FVC (%) and FEV1 (%). A novel microreactor was used to capture carbonyl compounds in the breath as direct output products. A machine learning workflow was implemented with the captured carbonyl compounds as input features for classification of diagnosis and disease severity based on PFT (DLCO and FVC normal/mild vs. moderate/severe; FEV1 normal/mild/moderate vs. moderately severe/severe). RESULTS: The proposed approach classified diagnosis with AUROC=0.877 ± 0.047 in the validation subsets. The AUROC was 0.820 ± 0.064, 0.898 ± 0.040, and 0.873 ± 0.051 for disease severity based on DLCO, FEV1, and FVC measurements, respectively. Eleven key carbonyl VOCs were identified with the potential to differentiate diagnosis and to classify severity. CONCLUSIONS: Exhaled breath carbonyl compounds can be linked to pulmonary function and fibrotic ILD diagnosis, moving towards improved pathophysiological understanding of pulmonary fibrosis.

Impulse Oscillometry as an Alternative Lung Function Test for Hospitalized Adults.

BACKGROUND: Impulse oscillometry (IOS) is a noninvasive technique that measures lung physiology independently of patient effort. In the present study, we aimed to investigate the utility of IOS parameters in comparison with pulmonary function testing (PFT) among hospitalized subjects, with emphasis on obstructive and small airway diseases. METHODS: Sixty-one subjects hospitalized either with unexplained dyspnea or for pre-surgery evaluation were included in the study. All subjects underwent PFTs and IOS test. The correlation between IOS results and PFTs was examined in different subgroups. The ability of IOS parameters to predict abnormal PFTs was evaluated using the area under the receiver operating characteristic (ROC) curve, and optimal cutoff values were calculated. RESULTS: IOS results were found to correlate with PFT values. Subgroup analysis revealed that these correlations were higher in younger (age < 70) and non-obese (body mass index < 25kg/m2) subjects. The resonant frequency was an independent predictor and had the best predictive ability for abnormal FEV1/FVC (area under the ROC curve 0.732 [95% CI 0.57-0.90], optimal cutoff 17 Hz, 87% sensitivity, 62% specificity) and abnormal forced expiratory flow during the middle half of the FVC maneuver (area under the ROC curve 0.667 [95% CI 0.53-0.81], optimal cutoff 15 Hz, 77% sensitivity, 54% specificity). Area of reactance and the difference in respiratory resistance at 5 Hz and 20 Hz also showed a good predictive ability for abnormal FEV1/FVC (area under the ROC curve 0.716 and 0.730, respectively). CONCLUSIONS: We found that the IOS performed well in diagnosing small airway and obstructive diseases among hospitalized subjects. IOS might serve as an alternative to standard PFTs in non-cooperative or dyspneic hospitalized patients.

Comparison of particles in exhaled air and multiple breath washout for assessment of small airway function in children with cystic fibrosis.

BACKGROUND: The introduction of modulator therapy for cystic fibrosis (CF) has led to an increased interest in the detection of small airway disease (SAD) as sensitive marker of treatment response. The particles in exhaled air (PExA) method, which records exhaled particle mass (PEx ng/L) and number (PExNR), detects SAD in adult patients. Our primary aim was to investigate if PExA outcomes in children with CF are different when compared to controls and associated with more severe disease. Secondary aims were to assess feasibility and repeatability of PExA in children with CF and to correlate PExA to multiple breath nitrogen washout (MBNW) as an established marker of SAD. METHODS: Thirteen healthy children (HC), 17 children with CF with normal lung function (CF-N) (FEV1 z-score ≥ -1.64) and six with airway obstruction (CF-AO) (FEV1 z-score < -1.64) between 8 and 18 years performed MBNW followed by PExA and spirometry. Children with CF repeated the measurements after 3 months. RESULTS: PEx ng/L and PExNR/L per liter of exhaled breath were similar between the three groups. The lung clearance index (LCI) was significantly higher in both CF-N and CF-AO compared to HC. All participants, except one, were able to perform PExA. Coefficient of variation for PEx ng/l was (median) 0.38, range 0-1.25 and PExNR/l 0.38, 0-1.09. Correlation between LCI and PEx ng/l was low, rs 0.32 (p = .07). CONCLUSION: PExA is feasible in children. In contrast to LCI, PExA did not differentiate healthy children from children with CF suggesting it to be a less sensitive tool to detect SAD.

Cardiopulmonary exercise testing in adolescence following extremely premature birth.

BACKGROUND: Although extremely premature birth disrupts lung development, adolescent survivors of extreme prematurity show good clinical and physiologic outcomes. Cardiopulmonary limitations may not be clinically evident at rest. Data regarding exercise limitation in adolescents following preterm birth in the postsurfactant era are limited. RESEARCH QUESTION: What are the long-term effects of bronchopulmonary dysplasia (BPD) and extreme prematurity (<29 weeks) on ventilatory response during exercise in adolescents in the postsurfactant era? STUDY DESIGN AND METHODS: We followed a longitudinally recruited cohort of children aged 13-19 years who were born at a gestational age of <29 weeks (study group - SG). We compared the cardiopulmonary exercise testing (CPET) results of those with and without BPD, to their own CPET results from elementary school age (mean 9.09 ± 1.05 years). RESULTS: Thirty-seven children aged 15.73 ± 1.31 years, mean gestational age 26 weeks ( ± 1.19), completed the study. CPET parameters in adolescence were within the normal range for age, including mean V̇O2 peak of 91% predicted. The BPD and non-BPD subgroups had similar results. In the longitudinal analysis of the SG, improvement was observed in adolescence, compared with elementary school age, in breathing reserve (36.37 ± 18.99 vs. 26.58 ± 17.92, p = 0.044), tidal volume as a fraction of vital capacity achieved at maximal load (0.51 ± 0.13 vs. 0.37 ± 0.08, p < 0.001), and respiratory exchange ratio at maximal load (1.18 ± 0.13 vs. 1.11 ± 0.10, p = 0.021). INTERPRETATION: In the current cohort, adolescents born extremely premature have essentially normal ventilatory response during exercise, unrelated to BPD diagnosis. CPET results in this population improve over time.

The impact of respiratory reactance in oscillometry on survival in patients with idiopathic pulmonary fibrosis.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a progressive disease with a poor prognosis. Pulmonary function tests (PFTs) aid in evaluating the disease status of IPF. The clinical significance of oscillometry measurements in interstitial lung diseases has recently been reported. Our previous study showed that respiratory reactance (Xrs) measured by oscillometry reflected disease severity and predicted subsequent lung capacity decline in patients with IPF. However, the direct impact of Xrs on survival needs to be determined, and there are currently no reference values in oscillometry to predict prognosis. Therefore, this study aimed to investigate the association between oscillometry measurements, particularly Xrs, and survival in patients with IPF and to determine the cutoff values of Xrs that predict 3-year survival. METHODS: We analyzed the relationship between the measured values of PFT and oscillometry derived from 178 patients with IPF. Univariate and multivariate Cox proportional hazards analyses were performed to investigate the relationships between clinical indices at the time of the first oscillometry and survival. We performed the time-dependent receiver operating characteristic (ROC) curve analysis to set the optimized cutoff values of Xrs for 3-year survival prediction. We examined the discriminating power of cutoff values of Xrs on survival using the Kaplan-Meier method and the log-rank test. RESULTS: Xrs components, especially in the inspiratory phase (In), significantly correlated with the PFT values. In the multivariate analyses, Xrs (all of reactance at 5 Hz [X5], resonant frequency [Fres], and low-frequency reactance area [ALX] in the inspiratory phase) had a significant impact on survival (X5, p = 0.003; Fres, p = 0.016; ALX, p = 0.003) independent of age, sex, and other prognostic factors derived from the univariate analysis. The area under the ROC curve was 0.765, 0.759, and 0.766 for X5 In, Fres In, and ALX In, with cutoff values determined at - 0.98, 10.67, and 5.32, respectively. We found significant differences in survival after dividing patients using each of the cutoff values of Xrs. CONCLUSIONS: In patients with IPF, Xrs measured by oscillometry significantly impacted survival. We also determined the cutoff values of Xrs to discriminate patients with poor prognoses.

Lung clearance index short-term variability in cystic fibrosis: a pre-post pulmonary exacerbation study.

BACKGROUND: Multiple Breath washout (MBW) represents an important tool to detect early a possible pulmonary exacerbation especially in Cystic Fibrosis (CF) disease. Lung clearance index (LCI) is the most commonly reported multiple breath washout (MBW) index and in the last years was used as management measure for evaluation. Our aim was to analyze clinical utility of LCI index variability in pulmonary exacerbation in CF after intravenous (IV) antibiotic therapy. METHODS: A single-center study was conducted at CF Unit of Bambino Gesù Children's Hospital among hospitalized > 3 years patients for pulmonary exacerbations and treated with antibiotic IV treatment for 14 days. MBW and spirometry were evaluated within 72 h of admission to hospital and at the end of hospitalization. Descriptive analysis was conducted and correlations between quantitative variables were investigated. RESULTS: Fifty-seven patients (M22/F35) with an average age 18.56 (± 8.54) years were enrolled. LCI2.5 was significantly reduced at the end of antibiotic treatment in both pediatric and adult populations with an average reduction of -6,99%; 37/57 patients denoted an improvement, 20/57 are stable or worsened in LCI2.5 values and 4/57 (7.02%) had a significant deterioration (> 15%) at end of treatment. On the contrary a significative elevation of FEV1 and FVC were found, respectively of + 7,30% and of + 5,46%. A positive good correlection among LCI 2.5 and Scond (rho = + 0,615, p = 0.000) and LCI 2.5 and Sacin (rho = + 0,649, p = 0.000) and a negative strong correlation between FEV1 and LCI 2.5 were found in post treatment period. A similar modification of LCI 2.5 and FEV1 was noticed in both adult and pediatric population. CONCLUSIONS: LCI may have a role in the routine clinical care of both adult and pediatric CF patients as a good tool to assess response to IV antibiotic end-therapy in the same way as FEV1.

Pulmonary Function Trajectories Over 6 Years and Their Determinants in Type 2 Diabetes: The Fremantle Diabetes Study Phase II.

OBJECTIVE: To assess whether there are clusters of people with type 2 diabetes with distinct temporal profiles of lung function changes and characteristics. RESEARCH DESIGN AND METHODS: Group-based trajectory modeling (GBTM) identified groups of participants with type 2 diabetes from the community-based observational Fremantle Diabetes Study Phase II (FDS2) who had at least two biennial measurements of forced expiratory volume in 1 s as a percentage of predicted (FEV1%pred) over 6 years. Independent associates of group membership were assessed using multinomial regression. RESULTS: Of 1,482 potential FDS2 participants, 1,074 (72.5%; mean age, 65.2 years; 45.5% female; median diabetes duration, 8.0 years) were included in the modeling. The best fitting GBTM model identified four groups categorized by FEV1%pred trajectory: high (19.5%; baseline FEV1%pred, 106.5 ± 9.5%; slope 0%/year), medium (47.7%; FEV1%pred, 87.3 ± 8.7%; slope, -0.32%/year), low (25.0%; baseline FEV1%pred, 68.9 ± 9.8%; slope, -0.72%/year), and very low (7.9%; baseline FEV1%pred, 48.8 ± 9.6%; slope, -0.68%/year). Compared with the high group, the other groups were characterized by nonmodifiable and modifiable risk factors associated with lung function decline in the general population (including ethnicity, marital status, smoking, obesity, coronary heart disease, and chronic respiratory disease). The main, diabetes-specific, significant predictor of group membership was a higher HbA1c in the very low group. There was a graded increase in mortality from 6.7% in the high group to 22.4% in the very low group. CONCLUSIONS: Measurement of lung function in type 2 diabetes could help optimize clinical management and improve prognosis, including addressing glycemic control in those with a very low FEV1%pred.

Diffusing Capacity as a Predictor of Hospitalizations in a Clinical Cohort of Chronic Obstructive Pulmonary Disease.

Rationale: Chronic obstructive pulmonary disease (COPD) hospitalizations are a major burden on patients. Diffusing capacity of the lung for carbon monoxide (DlCO) is a potential predictor that has not been studied in large cohorts. Objectives: This study used electronic health record data to evaluate whether clinically obtained DlCO predicts COPD hospitalizations. Methods: We performed time-to-event analyses of individuals with COPD and DlCO measurements from the Johns Hopkins COPD Precision Medicine Center of Excellence. Cox proportional hazard methods were used to model time from DlCO measurement to first COPD hospitalization and composite first hospitalization or death, adjusting for age, sex, race, body mass index, smoking status, forced expiratory volume in 1 second (FEV1), history of prior COPD hospitalization, and comorbidities. To identify the utility of including DlCO in risk models, area under the receiver operating curve (AUC) values were calculated for models with and without DlCO. Results were externally validated in a separate analogous cohort. Results: Of 2,793 participants, 368 (13%) had a COPD hospitalization within 3 years. In adjusted analyses, for every 10% decrease in DlCO% predicted, risk of COPD hospitalization increased by 10% (hazard ratio, 1.1; 95% confidence interval, 1.1-1.2; P < 0.001). Similar associations were observed for COPD hospitalizations or death. The model including demographics, comorbidities, FEV1, DlCO, and prior COPD hospitalizations performed well, with an AUC of 0.85 and an AUC of 0.84 in an external validation cohort. Conclusions: Diffusing capacity is a strong predictor of COPD hospitalizations in a clinical cohort of individuals with COPD, independent of airflow obstruction and prior hospitalizations. These findings support incorporation of DlCO in risk assessment of patients with COPD.

Robust imaging approach for precise prediction of postoperative lung function in lung cancer patients prior to curative operation.

BACKGROUND: To create a combined variable integrating both ventilation and perfusion as measured by preoperative dual-energy computed tomography (DECT), compare the results with predicted postoperative (PPO) lung function as estimated using conventional methods, and assess agreement with actual postoperative lung function. METHODS: A total of 33 patients with lung cancer who underwent curative surgery after DECT and perfusion scan were selected. Ventilation and perfusion values were generated from DECT data. In the "combined variable method," these two variables and clinical variables were linearly regressed to estimate PPO lung function. Six PPO lung function parameters (segment counting, perfusion scan, volume analysis, ventilation map, perfusion map, and combined variable) were compared with actual postoperative lung function using an intraclass correlation coefficient (ICC). RESULTS: The segment counting method produced the highest ICC for forced vital capacity (FVC) at 0.93 (p < 0.05), while the segment counting and perfusion map methods produced the highest ICC for forced expiratory volume in 1 second (FEV1 ; both 0.89, p < 0.05). The highest ICC value when using the combined variable method was for FEV1 /FVC (0.75, p < 0.05) and diffusing capacity of the lung for carbon monoxide (DLco; 0.80, p < 0.05) when using the perfusion map method. Overall, the perfusion map and ventilation map provided the best performance, followed by volume analysis, segment counting, perfusion scan, and the combined variable. CONCLUSIONS: Use of DECT image processing to predict postoperative lung function produced better agreement with actual postoperative lung function than conventional methods. The combined variable method produced ICC values of 0.8 or greater for FVC and FEV1 .

Impact on Pulmonary Function in a Randomized Trial of Single-Fraction and Multifraction Stereotactic Body Radiation Therapy for Pulmonary Oligometastatic Disease: An Analysis of TROG 13.01 (SAFRON II).

PURPOSE: The TROG 13.01 (SAFRON II) trial was a phase 2 multicenter trial comparing single-fraction (SF) and multifraction (MF) stereotactic body radiation therapy. Patients with 1 to 3 peripheral pulmonary oligometastases were randomized 1:1 between 28 Gy in 1 fraction and 48 Gy in 4 fractions. There were no differences between arms in efficacy or toxicity. We performed an analysis to assess changes in pulmonary function tests (PFTs) between arms over time and assessed the effect of the number and total volume of targets on PFT change over time. METHODS AND MATERIALS: A linear mixed model was used to describe the PFTs by treatment arm over time. The effect of number and volume of targets on PFTs at 6 and 12 months was assessed by a simple linear model. RESULTS: Ninety patients were randomized; 87 were treated for 133 pulmonary oligometastases. Forty-four were randomized to the SF arm and 43 to the MF arm. There were no differences in absolute or relative PFT measures of forced expiratory volume in 1 second (FEV1), diffusing capacity of the lungs for carbon monoxide (DLCO), or forced vital capacity (FVC) between the 2 arms. At 12 months, there was a reduction in absolute DLCO from baseline (-1.7 mL/min/mm Hg [95% CI, -2.5 to -1.0]), relative DLCO (-5.5% [95% CI, -8.4% to -2.6%]), absolute FEV1 (-0.17 L [95% CI, -0.23 to -0.11]), and absolute FVC (-0.20 L [95% CI, -0.27 to -0.13]). In patients with multiple pulmonary targets, increase in target number (per lesion) was associated with a reduction in the absolute FEV1 at 6 months of -0.10 L (95% CI, -0.18 to -0.03; P = .007), FEV1 at 12 months of -0.10 L (95% CI, -0.20 to -0.01; P = .04), FVC at 6 months of -0.11 L (95% CI, -0.20 to -0.03; P = .014), and FVC at 24 months of -0.13 L (95% CI, -0.25 to -0.01; P = .036). Reduction in FEV1 was also seen per 10-mL increase in PTV at 12 months (-0.03 L [95% CI, -0.06 to -0.00], P = .036). The number of targets and PTV were not associated with DLCO. CONCLUSIONS: Treating multiple targets resulted in increased loss of FEV1 and FVC but not DLCO. There were no significant differences in PFT decline between SF and MF stereotactic body radiation therapy.

Dysanapsis is not associated with exertional dyspnoea in healthy male and female never-smokers aged 40 years and older.

In healthy adults, airway-to-lung (i.e., dysanapsis) ratio is lower and dyspnoea during exercise at a given minute ventilation (V̇E) is higher in females than in males. We investigated the relationship between dysanapsis and sex on exertional dyspnoea in healthy adults. We hypothesized that females would have a smaller airway-to-lung ratio than males and that exertional dyspnoea would be associated with airway-to-lung ratio in males and females. We analyzed data from n = 100 healthy never-smokers aged ≥40 years enrolled in the Canadian Cohort Obstructive Lung Disease (CanCOLD) study who underwent pulmonary function testing, a chest computed tomography scan, and cardiopulmonary exercise testing. The luminal area of the trachea, right main bronchus, left main bronchus, right upper lobe, bronchus intermedius, left upper lobe, and left lower lobe were 22%-37% smaller (all p < 0.001) and the airway-to-lung ratio (i.e., average large conducting airway diameter relative to total lung capacity) was lower in females than in males (0.609 ± 0.070 vs. 0.674 ± 0.082; p < 0.001). During exercise, there was a significant effect of V̇E, sex, and their interaction on dyspnoea (all p < 0.05), indicating that dyspnoea increased as a function of V̇E to a greater extent in females than in males. However, after adjusting for age and total lung capacity, there were no significant associations between airway-to-lung ratio and measures of exertional dyspnoea, regardless of sex (all r < 0.34; all p > 0.05). Our findings suggest that sex differences in airway size do not contribute to sex differences in exertional dyspnoea.

Concentration-dependent alterations in the human plasma proteome following controlled exposure to diesel exhaust.

Traffic-related air pollution (TRAP) exposure is associated with systemic health effects, which can be studied using blood-based markers. Although we have previously shown that high TRAP concentrations alter the plasma proteome, the concentration-response relationship between blood proteins and TRAP is unexplored in controlled human exposure studies. We aimed to identify concentration-dependent plasma markers of diesel exhaust (DE), a model of TRAP. Fifteen healthy non-smokers were enrolled into a double-blinded, crossover study where they were exposed to filtered air (FA) and DE at 20, 50 and 150 µg/m3 PM2.5 for 4h, separated by ≥ 4-week washouts. We collected blood at 24h post-exposure and used label-free mass spectrometry to quantify proteins in plasma. Proteins exhibiting a concentration-response, as determined by linear mixed effects models (LMEMs), were assessed for pathway enrichment using WebGestalt. Top candidates, identified by sparse partial least squares discriminant analysis and LMEMs, were confirmed using enzyme-linked immunoassays. Thereafter, we assessed correlations between proteins that showed a DE concentration-response and acute inflammatory endpoints, forced expiratory volume in 1 s (FEV1) and methacholine provocation concentration causing a 20% drop in FEV1 (PC20). DE exposure was associated with concentration-dependent alterations in 45 proteins, which were enriched in complement pathways. Of the 9 proteins selected for confirmatory immunoassays, based on complementary bioinformatic approaches to narrow targets and availability of high-quality assays, complement factor I (CFI) exhibited a significant concentration-dependent decrease (-0.02 µg/mL per µg/m3 of PM2.5, p = 0.04). Comparing to FA at discrete concentrations, CFI trended downward at 50 (-2.14 ± 1.18, p = 0.08) and significantly decreased at 150 µg/m3 PM2.5 (-2.93 ± 1.18, p = 0.02). CFI levels were correlated with FEV1, PC20 and nasal interleukin (IL)-6 and IL-1ß. This study details concentration-dependent alterations in the plasma proteome following DE exposure at concentrations relevant to occupational and community settings. CFI shows a robust concentration-response and association with established measures of airway function and inflammation.

Spirometric patterns in young and middle-aged adults: a 20-year European study.

BACKGROUND: Understanding the natural history of abnormal spirometric patterns at different stages of life is critical to identify and optimise preventive strategies. We aimed to describe characteristics and risk factors of restrictive and obstructive spirometric patterns occurring before 40 years (young onset) and between 40 and 61 years (mid-adult onset). METHODS: We used data from the population-based cohort of the European Community Respiratory Health Survey (ECRHS). Prebronchodilator forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) were assessed longitudinally at baseline (ECRHS1, 1993-1994) and again 20 years later (ECRHS3, 2010-2013). Spirometry patterns were defined as: restrictive if FEV1/FVC≥LLN and FVC<10th percentile, obstructive if FEV1/FVC

Cystic lung disease in adult Indigenous Australians in the Northern Territory of Australia.

INTRODUCTION: Indigenous Australians have a high prevalence of chronic lung diseases. However, no previous studies have reported on cystic lung disease in an Indigenous patient cohort. METHODS: This report describes 20 adult Indigenous patients noted to have incidental lung cysts on chest computed tomography (CT) while being referred to undergo lung function tests in the Northern Territory of Australia. RESULTS: Of the total 20 Indigenous patients demonstrating presence of pulmonary cysts on chest CT scan, 13/20 (65%) were males with a mean age of 49.9 years (range 24-74 years), with no significant difference in age between males and females. The majority reported a smoking history and spirometry demonstrated moderate reduction in lung function parameters. While there was no pattern in the size or location of cysts, most demonstrated multiple cysts (55% had ≥5 cysts) with bilateral involvement (65%), alongside a range of concurrent pulmonary radiological abnormalities. The aetiology for lung cysts was largely unknown. CONCLUSION: This is the first report to illustrate cystic lung disease within an Indigenous population. Further radiology studies are required to investigate the causes and prognostications of cystic lung disease in Indigenous patients.