Impact of elexacaftor/tezacaftor/ivacaftor therapy on lung clearance index and magnetic resonance imaging in children with cystic fibrosis and one or two F508del alleles.

BACKGROUND: We recently demonstrated that elexacaftor/tezacaftor/ivacaftor (ETI) improves the lung clearance index (LCI) and abnormalities in lung morphology detected by magnetic resonance imaging (MRI) in adolescent and adult patients with cystic fibrosis (CF). However, real-world data on the effect of ETI on these sensitive outcomes of lung structure and function in school-age children with CF have not been reported. The aim of this study was therefore to examine the effect of ETI on the LCI and the lung MRI score in children aged 6-11 years with CF and one or two F508del alleles. METHODS: This prospective, observational, multicentre, post-approval study assessed the longitudinal LCI up to 12 months and the lung MRI score before and 3 months after initiation of ETI. RESULTS: A total of 107 children with CF including 40 heterozygous for F508del and a minimal function mutation (F/MF) and 67 homozygous for F508del (F/F) were enrolled in this study. Treatment with ETI improved the median (interquartile range (IQR)) LCI in F/MF (-1.0 (-2.0- -0.1); p<0.01) and F/F children (-0.8 (-1.9- -0.2); p<0.001) from 3 months onwards. Further, ETI improved the median (IQR) MRI global score in F/MF (-4.0 (-9.0-0.0); p<0.01) and F/F children (-3.5 (-7.3- -0.8); p<0.001). CONCLUSIONS: ETI improves early abnormalities in lung ventilation and morphology in school-age children with CF and at least one F508del allele in a real-world setting. Our results support early initiation of ETI to reduce or even prevent lung disease progression in school-age children with CF.

Bronchoscopic Measurement of Collateral Ventilation: State of the Art.

Endoscopic lung volume reduction procedure with valves is a well-studied treatment option for advanced lung emphysema to target lung hyperinflation in carefully selected patients with COPD. Before valve implantation, collateral ventilation (CV) of the target lobe needs to be assessed to obtain an optimal treatment effect. The analysis of CV according to current standards occurs via an in vivo assessment with the Chartis®system (PulmonX Inc., Redwood City, CA, USA) and a computed tomography (CT) scan of the thorax with interlobar fissure analysis. The focus of this review is to provide detailed information about the Chartis®procedure and interpretation of Chartis® phenotypes. As a main tool in the assessment of CV and being a safe procedure, the Chartis® assessment should be performed by default to confirm interlobar fissure analysis in most emphysema patients. Based on the obtained results, lung volume reduction therapy options should be discussed in an interdisciplinary emphysema conference.

Effects of Elexacaftor/Tezacaftor/Ivacaftor Therapy on Lung Clearance Index and Magnetic Resonance Imaging in Patients with Cystic Fibrosis and One or Two F508del Alleles.

Rationale: We recently demonstrated that triple-combination CFTR (cystic fibrosis transmembrane conductance regulator) modulator therapy with elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) improves CFTR function in airway and intestinal epithelia to 40-50% of normal in patients with cystic fibrosis (CF) with one or two F508del alleles. In previous studies, this improvement of CFTR function was shown to improve clinical outcomes; however, effects on the lung clearance index (LCI) determined by multiple-breath washout and abnormalities in lung morphology and perfusion detected by magnetic resonance imaging (MRI) have not been studied. Objectives: To examine the effect of ELX/TEZ/IVA on LCI and lung MRI scores in patients with CF and one or two F508del alleles aged ⩾12 years. Methods: This prospective, observational, multicenter, postapproval study assessed LCI and lung MRI scores before and 8-16 weeks after initiation of ELX/TEZ/IVA. Measurements and Main Results: A total of 91 patients with CF, including 45 heterozygous for F508del and a minimal function mutation (MF) and 46 homozygous for F508del, were enrolled in this study. Treatment with ELX/TEZ/IVA improved LCI in F508del/MF (-2.4; interquartile range [IQR], -3.7 to -1.1; P < 0.001) and F508del homozygous (-1.4; IQR, -2.4 to -0.4; P < 0.001) patients. Furthermore, ELX/TEZ/IVA improved the MRI global score in F508del/MF (-6.0; IQR, -11.0 to -1.3; P < 0.001) and F508del homozygous (-6.5; IQR, -11.0 to -1.3; P < 0.001) patients. Conclusions: Our data demonstrate that improvement of CFTR function by ELX/TEZ/IVA improves lung ventilation and abnormalities in lung morphology, including airway mucus plugging and wall thickening, in adolescent and adult patients with CF and one or two F508del alleles in a real-world, postapproval setting. Clinical trial registered with www.clinicaltrials.gov (NCT04732910).

Impact of Ventilation Modes on Bronchoscopic Chartis Assessment Outcome in Candidates for Endobronchial Valve Treatment.

BACKGROUND: Endobronchial valve therapy has proven to reduce lung hyperinflation and decrease disease burden in patients with severe lung emphysema. Exclusion of collateral ventilation (CV) of the targeted lobe by using an endobronchial assessment system (Chartis; PulmonX, Drive Redwood City, CA, USA) in combination with software-based fissure integrity analysis (FCS [fissure completeness score]) of computed tomography scans of the lung are established tools to select appropriate patients for endobronchial valve treatment. So far, there is no conclusive evidence if the ventilation mode during bronchoscopy impacts the outcome of Chartis assessments. METHODS: Patients with Chartis assessments and software-based quantification of FCS (StratX; PulmonX, Drive Redwood City, CA, USA) were enrolled in this retrospective study. During bronchoscopy, pulmonary fissure integrity was evaluated with the Chartis assessment system in each patient first under spontaneous breathing and subsequently under high-frequency (HF) jet ventilation. RESULTS: In total, 102 patients were analyzed. Four Chartis phenotypes CV positive (CV+), CV negative (CV-), low flow, and low plateau in spontaneous breathing and HF jet ventilation were identified. The frequency of each Chartis phenotype per lobe was similar in both settings. When comparing Chartis assessments in spontaneous breathing and HF jet ventilation, there was an overall good concordance rate for all analyzed fissures. In agreement, receiver operating characteristic analysis of the FCS showed an almost similar prediction for CV+ and CV- status independent of the ventilation modes. CONCLUSION: Chartis assessment in spontaneous breathing and HF jet ventilation had similar rates in detecting CV in lung emphysema. Our results suggest that both modes are equivalent for the assessment of CV.

Outcomes of Endobronchial Valve Treatment Based on the Precise Criteria of an Endobronchial Catheter for Detection of Collateral Ventilation under Spontaneous Breathing.

BACKGROUND: Endoscopic lung volume reduction with valves is a valid therapeutic option for COPD patients with severe emphysema. The exclusion of interlobar collateral ventilation (CV) is an important predictor of clinical success. OBJECTIVES: Recently, a catheter-based endobronchial in vivo measurement system (Chartis, Pulmonx, USA) has become routine in the clinical evaluation of CV status in target lobes, but the criteria for phenotyping CV by Chartis evaluation have not yet been defined. We asked the questions, how many phenotypes can be identified using Chartis, what are the exact criteria to distinguish them, and how do the Chartis phenotypes respond to valve insertion? METHODS: In a retrospective study, 406 Chartis assessments of 166 patients with severe COPD were analyzed. Four Chartis phenotypes, CV positive (CV+), CV negative (CV-), low flow (LF) and low plateau were identified. Fifty-two patients without CV were treated with valves and followed for 3 months. RESULTS: The Chartis phenotypes were discriminated with respect to decline in expiratory peak flow, increase in resistance index and change in total exhaled volume after 1, 2, 3, 4 and 5 min of measurement time (p < 0.0001, ANOVA), and the cutoff criteria were defined accordingly. To examine the application of these phenotyping criteria, students applied them to 100 Chartis assessments, and they demonstrated almost perfect inter- and intraobserver agreements (x03BA; > 0.9). Compared to baseline, CV- and LF patients with ipsilateral CV- lobe showed an improvement in FEV1 (p < 0.05), vital capacity (p < 0.05) and target lobe volume reduction (p < 0.005) after valve insertion. CONCLUSION: This study describes the most prevalent Chartis phenotypes.

Predicting Lung Volume Reduction after Endobronchial Valve Therapy Is Maximized Using a Combination of Diagnostic Tools.

BACKGROUND: Bronchoscopic lung volume reduction using one-way endobronchial valves (EBVs) has been proven to be effective in patients with severe emphysema. However, the selection of patients without collateral ventilation prior to treatment is critical for procedural success. Collateral ventilation can be assessed directly with the Chartis system or indirectly using computed tomography (CT) fissure analysis. OBJECTIVES: We retrospectively evaluated the diagnostic value of a combination of the quantitative CT interlobar fissure completeness score (FCS) and Chartis in predicting responders to EBV therapy. METHODS: CT data from four prospective studies were pooled and analyzed using semiautomated software to quantify the completeness of interlobar fissures. These FCSs were compared to a reference standard of achieving ≥350 ml of target lobe volume reduction after EBV treatment. Using a receiver operating characteristic curve, optimal thresholds predictive of complete fissures (responders) and incomplete fissures (non-responders) were determined. A subgroup of patients with partially complete fissures was identified, where software had lower accuracy. The complementary value of Chartis was investigated in this group. RESULTS: A fissure was defined as complete (FCS >95%), incomplete (FCS <80%), or partially complete (80% < FCS < 95%). The positive predictive value (PPV) of complete fissures is 88.1%, and the negative predictive value (NPV) is 92.9%, with an overall accuracy of 89.2%. Chartis was utilized in patients with partially complete fissures, with a PPV of 82.3%, an NPV of 84.6%, and an accuracy of 83.3%. CONCLUSION: Combining diagnostic tools could reduce the burden on patients and the healthcare system while providing clinicians with a better means for patient selection for EBV therapy.

Contrast agent-free functional magnetic resonance imaging with matrix pencil decomposition to quantify abnormalities in lung perfusion and ventilation in patients with cystic fibrosis.

Background: Previous studies showed that contrast-enhanced (CE) morpho-functional magnetic resonance imaging (MRI) detects abnormalities in lung morphology and perfusion in patients with cystic fibrosis (CF). Novel matrix pencil decomposition MRI (MP-MRI) enables quantification of lung perfusion and ventilation without intravenous contrast agent administration. Objectives: To compare MP-MRI with established morpho-functional MRI and spirometry in patients with CF. Methods: Thirty-nine clinically stable patients with CF (mean age 21.6 ± 10.7 years, range 8-45 years) prospectively underwent morpho-functional MRI including CE perfusion MRI, MP-MRI and spirometry. Two blinded chest radiologists assessed morpho-functional MRI and MP-MRI employing the validated chest MRI score. In addition, MP-MRI data were processed by automated software calculating perfusion defect percentage (QDP) and ventilation defect percentage (VDP). Results: MP perfusion score and QDP correlated strongly with the CE perfusion score (both r = 0.81; p < 0.01). MP ventilation score and VDP showed strong inverse correlations with percent predicted FEV1 (r = -0.75 and r = -0.83; p < 0.01). The comparison of visual and automated parameters showed that both MP perfusion score and QDP, and MP ventilation score and VDP were strongly correlated (r = 0.74 and r = 0.78; both p < 0.01). Further, the MP perfusion score and MP ventilation score, as well as QDP and VDP were strongly correlated (r = 0.88 and r = 0.86; both p < 0.01). Conclusion: MP-MRI detects abnormalities in lung perfusion and ventilation in patients with CF without intravenous or inhaled contrast agent application, and correlates strongly with the well-established CE perfusion MRI score and spirometry. Automated analysis of MP-MRI may serve as quantitative noninvasive outcome measure for diagnostic monitoring and clinical trials.

Long-Term Impact of Lumacaftor/Ivacaftor Treatment on Cystic Fibrosis Disease Progression in Children 2-5 Years of Age Homozygous for F508del-CFTR: A Phase 2, Open-Label Clinical Trial.

Rationale: Clinical trials show that lumacaftor/ivacaftor (LUM/IVA) treatment has the potential to modify early cystic fibrosis (CF) disease progression in children as young as 2 years of age. Objectives: To assess the long-term impact of LUM/IVA treatment on CF disease progression in children aged 2-5 years. Methods: This phase 2 trial had two parts: part 1, a 48-week, randomized, double-blind, placebo-controlled study of LUM/IVA in children aged 2-5 years (previously reported) was followed by a 48-week open-label treatment period in which all children received LUM/IVA (part 2; reported here). Endpoints assessed in part 2 included absolute changes from baseline in chest magnetic resonance imaging (MRI) global score at Week 96; weight-for-age, stature-for-age, and body mass index (BMI)-for-age z-scores at Week 96; lung clearance index based on lung volume turnover required to reach 2.5% of starting N2 concentration (LCI2.5) through Week 96; chest MRI morphological score, chest MRI perfusion score, weight, stature, BMI, and microbiology cultures (oropharyngeal swabs) at Week 96; sweat chloride, amount of immunoreactive trypsinogen, fecal elastase-1 concentration, and fecal calprotectin through Week 96; and number of pulmonary exacerbations, time to first pulmonary exacerbation, and number of CF-related hospitalizations. Results: Forty-nine children received one or more doses of LUM/IVA in the open-label period (33 in the LUM/IVA to LUM/IVA group and 16 in the placebo to LUM/IVA group), with a mean exposure of 47.1 (standard deviation [SD], 5.2) weeks. The mean absolute change in MRI global score (negative value indicates improvement) from baseline at Week 96 was -2.7 (SD, 7.0; 95% confidence interval [CI], -5.2 to -0.1) in the LUM/IVA to LUM/IVA group and -5.6 (SD, 6.9; 95% CI, -9.2 to -1.9) in the placebo to LUM/IVA group. Improvements in LCI2.5, sweat chloride concentration, and markers of pancreatic function and intestinal inflammation were also observed in both groups. Growth parameters remained stable in both groups. The majority of children had adverse events considered mild (38.8%) or moderate (40.8%). Two (4.1%) children discontinued LUM/IVA treatment because of adverse events (distal intestinal obstruction syndrome [n = 1] and alanine aminotransferase increase [n = 1]). Conclusions: These findings confirm the potential for early LUM/IVA treatment to alter the trajectory of CF disease progression, including CF lung disease, in children as young as 2 years of age. Clinical trial registered with ClinicalTrials.gov (NCT03625466).

Effects of Lumacaftor/Ivacaftor on Cystic Fibrosis Disease Progression in Children 2 through 5 Years of Age Homozygous for F508del-CFTR: A Phase 2 Placebo-controlled Clinical Trial.

Rationale: Lumacaftor/ivacaftor (LUM/IVA) was shown to be safe and well tolerated in children 2 through 5 years of age with cystic fibrosis (CF) homozygous for F508del-CFTR in a Phase 3 open-label study. Improvements in sweat chloride concentration, markers of pancreatic function, and lung clearance index2.5 (LCI2.5), along with increases in growth parameters, suggested the potential for early disease modification with LUM/IVA treatment. Objective: To further assess the effects of LUM/IVA on CF disease progression in children 2 through 5 years of age using chest magnetic resonance imaging (MRI). Methods: This Phase 2 study had two parts: a 48-week, randomized, double-blind, placebo-controlled treatment period in which children 2 through 5 years of age with CF homozygous for F508del-CFTR received either LUM/IVA or placebo (Part 1) followed by an open-label period in which all children received LUM/IVA for an additional 48 weeks (Part 2). The results from Part 1 are reported. The primary endpoint was absolute change from baseline in chest MRI global score at Week 48. Secondary endpoints included absolute change in LCI2.5 through Week 48 and absolute changes in weight-for-age, stature-for-age, and body mass index-for-age z-scores at Week 48. Additional endpoints included absolute changes in sweat chloride concentration, fecal elastase-1 levels, serum immunoreactive trypsinogen, and fecal calprotectin through Week 48. The primary endpoint was analyzed using Bayesian methods, where the actual Bayesian posterior probability of LUM/IVA being superior to placebo in the chest MRI global score at Week 48 was calculated using a vague normal prior distribution; secondary and additional endpoints were analyzed using descriptive summary statistics. Results: Fifty-one children were enrolled and received LUM/IVA (n = 35) or placebo (n = 16). For the change in chest MRI global score at Week 48, the Bayesian posterior probability of LUM/IVA being better than placebo (treatment difference, <0; higher score indicates greater abnormality) was 76%; the mean treatment difference was -1.5 (95% credible interval, -5.5 to 2.6). Treatment with LUM/IVA also led to within-group numerical improvements in LCI2.5, growth parameters, and biomarkers of pancreatic function as well as greater decreases in sweat chloride concentration compared with placebo from baseline through Week 48. Safety data were consistent with the established safety profile of LUM/IVA. Conclusions: This placebo-controlled study suggests the potential for early disease modification with LUM/IVA treatment, including that assessed by chest MRI, in children as young as 2 years of age. Clinical trial registered with www.clinicaltrials.gov (NCT03625466).

When Treatment of Pulmonary Emphysema with Endobronchial Valves Did Not Work: Evaluation of Quantitative CT Analysis and Pulmonary Function Tests Before and After Valve Explantation.

Purpose: To investigate changes in quantitative CT analysis (QCT) and pulmonary function tests (PFT) in pulmonary emphysema patients who required premature removal of endobronchial valves (EBV). Patients and Methods: Our hospital's medical records listed 274 patients with high-grade COPD (GOLD stages 3 and 4) and pulmonary emphysema who were treated with EBV to reduce lung volume. Prior to intervention, a complete evaluation was performed that included quantitative computed tomography analysis (QCT) of scans acquired at full inspiration and full expiration, pulmonary function tests (PFT), and paraclinical findings (6-minute walking distance test (6MWDT) and quality of life questionnaires). In 41 of these 274 patients, EBV treatment was unsuccessful and the valves had to be removed for various reasons. A total of 10 of these 41 patients ventured a second attempt at EBV therapy and underwent complete reevaluation. In our retrospective study, results from three time points were compared: Before EBV implantation (BL), after EBV implantation (TP2), and after EBV explantation (TP3). QCT parameters included lung volume, total emphysema score (TES, ie, the emphysema index) and the 15th percentile of lung attenuation (P15) for the whole lung and each lobe separately. Differences in these parameters between inspiration and expiration were calculated (Vol. Diff (%), TES Diff (%), P15 Diff (%)). The results of PFT and further clinical tests were taken from the patient's records. Results: We found persistent therapy effect in the target lobe even after valve explantation together with a compensatory hyperinflation of the rest of the lung. As a result of these two divergent effects, the volume of the total lung remained rather constant. Furthermore, there was a slight deterioration of the emphysema score for the whole lung, whereas the TES of the target lobe persistently improved. Conclusion: Interestingly, we found evidence that, contrary to our expectations, unsuccessful EBV therapy can have a persistent positive effect on target lobe QCT scores.

Severity of respiratory failure and computed chest tomography in acute COVID-19 correlates with pulmonary function and respiratory symptoms after infection with SARS-CoV-2: An observational longitudinal study over 12 months.

INTRODUCTION: Prospective and longitudinal data on pulmonary injury over one year after acute coronavirus disease 2019 (COVID-19) are sparse. We aim to determine reductions in pulmonary function and respiratory related quality of life up to 12 months after acute COVID-19. METHODS: Patients with acute COVID-19 were enrolled into an ongoing single-centre, prospective observational study and prospectively examined 6 weeks, 3, 6 and 12 months after onset of COVID-19 symptoms. Chest CT-scans, pulmonary function and symptoms assessed by St. Georges Respiratory Questionnaire were used to evaluate respiratory limitations. Patients were stratified according to severity of acute COVID-19. RESULTS: Median age of all patients was 57 years, 37.8% were female. Higher age, male sex and higher BMI were associated with acute-COVID-19 severity (p < 0.0001, 0.001 and 0.004 respectively). Also, pulmonary restriction and reduced carbon monoxide diffusion capacity was associated with disease severity. In patients with restriction and impaired diffusion capacity, FVC improved over 12 months from 61.32 to 71.82, TLC from 68.92 to 76.95, DLCO from 60.18 to 68.98 and KCO from 81.28 to 87.80 (percent predicted values; p = 0.002, 0.045, 0.0002 and 0.0005). The CT-score of lung involvement in the acute phase was associated with restriction and reduction in diffusion capacity in follow-up. Respiratory symptoms improved for patients in higher severity groups during follow-up, but not for patients with initially mild disease. CONCLUSION: Severity of respiratory failure during COVID-19 correlates with the degree of pulmonary function impairment and respiratory quality of life in the year after acute infection.

A reporting and analysis framework for structured evaluation of COVID-19 clinical and imaging data.

The COVID-19 pandemic has worldwide individual and socioeconomic consequences. Chest computed tomography has been found to support diagnostics and disease monitoring. A standardized approach to generate, collect, analyze, and share clinical and imaging information in the highest quality possible is urgently needed. We developed systematic, computer-assisted and context-guided electronic data capture on the FDA-approved mint LesionTM software platform to enable cloud-based data collection and real-time analysis. The acquisition and annotation include radiological findings and radiomics performed directly on primary imaging data together with information from the patient history and clinical data. As proof of concept, anonymized data of 283 patients with either suspected or confirmed SARS-CoV-2 infection from eight European medical centers were aggregated in data analysis dashboards. Aggregated data were compared to key findings of landmark research literature. This concept has been chosen for use in the national COVID-19 response of the radiological departments of all university hospitals in Germany.

Quantitative CT Analysis in Patients with Pulmonary Emphysema: Do Calculated Differences Between Full Inspiration and Expiration Correlate with Lung Function?

Purpose: The aim of this retrospective study was to evaluate correlations between parameters of quantitative computed tomography (QCT) analysis, especially the 15th percentile of lung attenuation (P15), and parameters of clinical tests in a large group of patients with pulmonary emphysema. Patients and Methods: One hundred and seventy-two patients with pulmonary emphysema and chronic obstructive pulmonary disease (COPD) global initiative for chronic obstructive lung disease (GOLD) stage 3 or 4 were assessed by nonenhanced thin-section CT scans in full inspiratory and expiratory breath-hold, pulmonary function test (PFT), a 6-minute walk test (6MWT), and quality of life questionnaires (SGRQ and CAT). QCT parameters included total lung volume (TLV), total emphysema score (TES), and P15, all measured at inspiration (IN) and expiration (EX). Differences between inspiration and expiration were calculated for TLV (TLVDiff), TES (TESDiff), and P15 (P15Diff). Spearman correlation analysis was performed. Results: CT-measured lung volume in inspiration (TLVIN) correlated strongly with spirometry-measured total lung capacity (TLC) (r=0.81, p<0.001) and moderately to strongly with residual volume (RV), forced vital capacity (FVC), and forced expiratory volume in 1 second (FEV1)/FVC (r=0.60, 0.56, and -0.49, each p<0.001). Lung volume in expiration (TLVEX) correlated moderately to strongly with TLC, RV and FEV1/FVC ratio (r=0.75, 0.66, and -0.43, each p<0.001). TES and P15 showed stronger correlations with the carbon monoxide transfer coefficient (KCO%) (r= -0.42, 0.44, both p<0.001), when measured during expiration. P15Diff correlated moderately with KCO% and carbon monoxide diffusing capacity (DLCO%) (r= 0.41, 0.40, both p<0.001). The 6MWT and most QCT parameters showed significant differences between COPD GOLD 3 and 4 groups. Conclusion: Our results suggest that QCT can help predict the severity of lung function decrease in patients with pulmonary emphysema and COPD GOLD 3 or 4. Some QCT parameters, including P15EX and P15Diff, correlated moderately to strongly with parameters of pulmonary function tests.

An Integrative Approach of the Fissure Completeness Score and Chartis Assessment in Endobronchial Valve Treatment for Emphysema.

Purpose: Lung volume reduction using one-way endobronchial valves is a bronchoscopic treatment for patients with severe emphysema without collateral ventilation between the treatment target lobe and the ipsilateral lobe(s). CT-scan fissure analysis is often used as a surrogate to predict the absence of collateral ventilation. We aimed to evaluate the predictive value of the fissure completeness score (FCS) compared to the functional Chartis measurement of collateral ventilation and to provide cut-off values of the FCS in patient selection. Patients and Methods: Multicenter study in patients eligible for treatment with one-way valves. The FCS was calculated by quantitative CT analysis (Thirona, the Netherlands) and compared to status of interlobar collateral ventilation measured with Chartis system (PulmonX, USA). Thresholds were calculated for the predictive values of the presence of collateral ventilation. Results: An FCS >95% of the left major fissure had a positive predictive value (PPV) of 91%, with 1 in 11 fissures demonstrating collateral ventilation with Chartis measurement, whereas an FCS of ≤80% had a negative predictive value (NPV) of 100% for the presence of collateral ventilation. For the right major fissure, the NPV was 100% for an FCS ≤90%, but 69.7% for the right upper lobe fissure. Conclusion: Quantitative CT analysis is recommended in all patients evaluated for endobronchial valves. Patients with incomplete fissures (left major fissure: FCS <80%; right major fissure: <90%) can be excluded from Chartis measurement and endobronchial valve treatment. In patients with more complete fissures, the FCS is not specific enough for endobronchial valve treatment decisions. In this case, additional Chartis measurements are always recommended in the right lung. For the left lung, Chartis assessments may be omitted if the FCS is >95%.

Evaluation of PEEP and prone positioning in early COVID-19 ARDS.

BACKGROUND: In face of the Coronavirus Disease (COVID)-19 pandemic, best practice for mechanical ventilation in COVID-19 associated Acute Respiratory Distress Syndrome (ARDS) is intensely debated. Specifically, the rationale for high positive end-expiratory pressure (PEEP) and prone positioning in early COVID-19 ARDS has been questioned. METHODS: The first 23 consecutive patients with COVID-19 associated respiratory failure transferred to a single ICU were assessed. Eight were excluded: five were not invasively ventilated and three received veno-venous ECMO support. The remaining 15 were assessed over the first 15 days of mechanical ventilation. Best PEEP was defined by maximal oxygenation and was determined by structured decremental PEEP trials comprising the monitoring of oxygenation, airway pressures and trans-pulmonary pressures. In nine patients the impact of prone positioning on oxygenation was investigated. Additionally, the effects of high PEEP and prone positioning on pulmonary opacities in serial chest x-rays were determined by applying a semiquantitative scoring-system. This investigation is part of the prospective observational PA-COVID-19 study. FINDINGS: Patients responded to initiation of invasive high PEEP ventilation with markedly improved oxygenation, which was accompanied by reduced pulmonary opacities within 6 h of mechanical ventilation. Decremental PEEP trials confirmed the need for high PEEP (17.9 (SD ± 3.9) mbar) for optimal oxygenation, while driving pressures remained low. Prone positioning substantially increased oxygenation (p<0.01). INTERPRETATION: In early COVID-19 ARDS, substantial PEEP values were required for optimizing oxygenation. Pulmonary opacities resolved during mechanical ventilation with high PEEP suggesting recruitment of lung volume. FUNDING: German Research Foundation, German Federal Ministry of Education and Research.

Selecting Patients for Lobar Lung Volume Reduction Therapy: What Quantitative Computed Tomography Parameters Matter?

PURPOSE: Evaluation of emphysema distribution with quantitative computed tomography (qCT) prior to endoscopic lung volume reduction (ELVR) is recommended. The aim of this study was to determine which of the commonly assessed qCT parameters prior to endoscopic lung volume reduction (ELVR) best predicts outcome of treatment. MATERIALS AND METHODS: 50 patients who underwent technically successful ELVR at our institution were retrospectively analyzed. We performed quantitative analysis of the CT scans obtained prior to ELVR and carried out Mann-Whitney U-tests and a logistic regression analysis to identify the qCT parameters that predict successful outcome of ELVR in terms of improved forced expiratory volume in 1 second (FEV1). RESULTS: In the Mann-Whitney U-test, the interlobar emphysema heterogeneity index (p = 0.008) and the pulmonary emphysema score (p = 0.022) showed a statistically significant difference between responders and non-responders. In multiple logistic regression analysis only the interlobar emphysema heterogeneity index (p = 0.008) showed a statistically significant impact on the outcome of ELVR, while targeted lobe volume, total lung volume, targeted lobe emphysema score and total lung emphysema score did not. CONCLUSION: Of all commonly assessed quantitative CT parameters, only the heterogeneity index definitely allows prediction of ELVR outcome in patients with advanced chronic obstructive pulmonary disease (COPD). KEY POINTS: · Quantitative CT is recommended prior to ELVR.. · The relevance of the obtained parameters from quantitative CT remains controversial.. · This study confirms that only the emphysema heterogeneity index has a definite impact.. CITATION FORMAT: · Theilig DC, Huebner R, Neumann K et al. Selecting Patients for Lobar Lung Volume Reduction Therapy: What Quantitative Computed Tomography Parameters Matter?. Fortschr Röntgenstr 2019; 191: 40 - 47.

Quantitative CT analysis in patients with pulmonary emphysema: is lung function influenced by concomitant unspecific pulmonary fibrosis?

Purpose: Quantitative analysis of CT scans has proven to be a reproducible technique, which might help to understand the pathophysiology of chronic obstructive pulmonary disease (COPD) and combined pulmonary fibrosis and emphysema. The aim of this retrospective study was to find out if the lung function of patients with COPD with Global Initiative for Chronic Obstructive Lung Disease (GOLD) stages III or IV and pulmonary emphysema is measurably influenced by high attenuation areas as a correlate of concomitant unspecific fibrotic changes of lung parenchyma. Patients and methods: Eighty-eight patients with COPD GOLD stage III or IV underwent CT and pulmonary function tests. Quantitative CT analysis was performed to determine low attenuation volume (LAV) and high attenuation volume (HAV), which are considered to be equivalents of fibrotic (HAV) and emphysematous (LAV) changes of lung parenchyma. Both parameters were determined for the whole lung, as well as peripheral and central lung areas only. Multivariate regression analysis was used to correlate HAV with different parameters of lung function. Results: Unlike LAV, HAV did not show significant correlation with parameters of lung function. Even in patients with a relatively high HAV of more than 10%, in contrast to HAV (p=0.786) only LAV showed a significantly negative correlation with forced expiratory volume in 1 second (r=-0.309, R2=0.096, p=0.003). A severe decrease of DLCO% was associated with both larger HAV (p=0.045) and larger LAV (p=0.001). Residual volume and FVC were not influenced by LAV or HAV. Conclusion: In patients with COPD GOLD stage III-IV, emphysematous changes of lung parenchyma seem to have such a strong influence on lung function, which is a possible effect of concomitant unspecific fibrosis is overwhelmed.

Comparison of distinctive models for calculating an interlobar emphysema heterogeneity index in patients prior to endoscopic lung volume reduction.

BACKGROUND: The degree of interlobar emphysema heterogeneity is thought to play an important role in the outcome of endoscopic lung volume reduction (ELVR) therapy of patients with advanced COPD. There are multiple ways one could possibly define interlobar emphysema heterogeneity, and there is no standardized definition. PURPOSE: The aim of this study was to derive a formula for calculating an interlobar emphysema heterogeneity index (HI) when evaluating a patient for ELVR. Furthermore, an attempt was made to identify a threshold for relevant interlobar emphysema heterogeneity with regard to ELVR. PATIENTS AND METHODS: We retrospectively analyzed 50 patients who had undergone technically successful ELVR with placement of one-way valves at our institution and had received lung function tests and computed tomography scans before and after treatment. Predictive accuracy of the different methods for HI calculation was assessed with receiver-operating characteristic curve analysis, assuming a minimum difference in forced expiratory volume in 1 second of 100 mL to indicate a clinically important change. RESULTS: The HI defined as emphysema score of the targeted lobe (TL) minus emphysema score of the ipsilateral nontargeted lobe disregarding the middle lobe yielded the best predicative accuracy (AUC =0.73, P=0.008). The HI defined as emphysema score of the TL minus emphysema score of the lung without the TL showed a similarly good predictive accuracy (AUC =0.72, P=0.009). Subgroup analysis suggests that the impact of interlobar emphysema heterogeneity is of greater importance in patients with upper lobe predominant emphysema than in patients with lower lobe predominant emphysema. CONCLUSION: This study reveals the most appropriate ways of calculating an interlobar emphysema heterogeneity with regard to ELVR.

Differences of airway dimensions between patients with and without bronchiolitis obliterans syndrome after lung transplantation-Computer-assisted quantification of computed tomography.

BACKGROUND: The aim of our retrospective study was to determine whether a dedicated software for assessment of airway morphology can detect differences in airway dimensions between patients with and without bronchiolitis obliterans syndrome (BOS), regarded as the clinical correlate of chronic lung allograft rejection. METHODS: 12 patients with and 14 patients without diagnosis of BOS were enrolled in the study. Evaluation of bronchial wall area percentage (WA%) and bronchial wall thickness (WT) in all follow-up CT scans was performed using a semiautomatic airway assessment tool. We assessed temporal changes (ΔWA%, ΔWT) and compared these morphological parameters with forced expiratory volume in one second (ΔFEV1). RESULTS: In patients with and without BOS, the temporal changes over the entire follow-up were 26.6% versus 16.2% for ΔFEV1 (p=0.034), 14.2% versus 5.4% for ΔWA% (p=0.003) and 0.212mm versus 0.064mm for ΔWT (p=0.011). CONCLUSIONS: We detected significant differences of the temporal changes of airway dimensions (ΔWA%, ΔWT) between lung transplant recipients with and without BOS. We conclude that computer-assisted bronchial wall measurements in CT scans might complement the information from pulmonary function tests and establish as a non-invasive method to confirm BOS in lung transplant recipients in the future.

Lung perfusion and emphysema distribution affect the outcome of endobronchial valve therapy.

The exclusion of collateral ventilation (CV) and other factors affect the clinical success of endoscopic lung volume reduction (ELVR). However, despite its benefits, the outcome of ELVR remains difficult to predict. We investigated whether clinical success could be predicted by emphysema distribution assessed by computed tomography scan and baseline perfusion assessed by perfusion scintigraphy. Data from 57 patients with no CV in the target lobe (TL) were retrospectively analyzed after ELVR with valves. Pulmonary function tests (PFT), St George's Respiratory Questionnaire (SGRQ), and 6-minute walk tests (6MWT) were performed on patients at baseline. The sample was grouped into high and low levels at the median of TL perfusion, ipsilateral nontarget lobe (INL) perfusion, and heterogeneity index (HI). These groups were analyzed for association with changes in outcome parameters from baseline to 3 months follow-up. Compared to baseline, patients showed significant improvements in PFT, SGRQ, and 6MWT (all P≤0.001). TL perfusion was not associated with changes in the outcome. High INL perfusion was significantly associated with increases in 6MWT (P=0.014), and high HI was associated with increases in forced expiratory volume in 1 second (FEV1), (P=0.012). Likewise, there were significant correlations for INL perfusion and improvement of 6MWT (r=0.35, P=0.03) and for HI and improvement in FEV1 (r=0.45, P=0.001). This study reveals new attributes that associate with positive outcomes for patient selection prior to ELVR. Patients with high perfusions in INL demonstrated greater improvements in 6MWT, while patients with high HI were more likely to respond in FEV1.