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Rationale: Chest computed tomography (CT) scans are essential to diagnose and monitor bronchiectasis (BE). To date, few quantitative data are available about the nature and extent of structural lung abnormalities (SLAs) on CT scans of patients with BE. Objectives: To investigate SLAs on CT scans of patients with BE and the relationship of SLAs to clinical features using the EMBARC (European Multicenter Bronchiectasis Audit and Research Collaboration) registry. Methods: CT scans from patients with BE included in the EMBARC registry were analyzed using the validated Bronchiectasis Scoring Technique for CT (BEST-CT). The subscores of this instrument are expressed as percentages of total lung volume. The items scored are atelectasis/consolidation, BE with and without mucus plugging (MP), airway wall thickening, MP, ground-glass opacities, bullae, airways, and parenchyma. Four composite scores were calculated: total BE (i.e., BE with and without MP), total MP (i.e., BE with MP plus MP alone), total inflammatory changes (i.e., atelectasis/consolidation plus total MP plus ground-glass opacities), and total disease (i.e., all items but airways and parenchyma). Measurements and Main Results: CT scans of 524 patients with BE were analyzed. Mean subscores were 4.6 (range, 2.3–7.7) for total BE, 4.2 (1.2–8.1) for total MP, 8.3 (3.5–16.7) for total inflammatory changes, and 14.9 (9.1–25.9) for total disease. BE associated with primary ciliary dyskinesia was associated with more SLAs, whereas chronic obstructive pulmonary disease was associated with fewer SLAs. Lower FEV1, longer disease duration, Pseudomonas aeruginosa and nontuberculous mycobacterial infections, and severe exacerbations were all independently associated with worse SLAs. Conclusions: The type and extent of SLAs in patients with BE are highly heterogeneous. Strong relationships between radiological disease and clinical features suggest that CT analysis may be a useful tool for clinical phenotyping. [ABSTRACT FROM AUTHOR]

Rationale: Clinical trials have shown that use of elexacaftor/ tezacaftor/ivacaftor (ETI) is associated with improvements in sweat chloride, pulmonary function, nutrition, and quality of life in people with cystic fibrosis (CF). Little is known about the impact of ETI on ventilation inhomogeneity and lung structure. Objectives: RECOVER is a real-world study designed to measure the impact of ETI in people with CF. The primary endpoints were lung clearance (lung clearance index; LCI2.5) and FEV1. Secondary endpoints included spirometry-controlled chest computed tomography (CT) scores. Methods: The study was conducted in seven sites in Ireland and the United Kingdom. Participants ages 12 years and older who were homozygous for the F508del mutation (F508del/F508del) or heterozygous for F508del and a minimum-function mutation (F508del/MF) were recruited before starting ETI and were followed up over 12 months. LCI2.5 was measured using nitrogen multiple breath washout (MBW) at baseline and at 6 and 12 months. Spirometry was performed as per the criteria of the American Thoracic Society and the European Respiratory Society. Spirometry-controlled chest CT scans were performed at baseline and at 12 months. CT scans were scored using the Perth Rotterdam Annotated Grid Morphometric Analysis (PRAGMA) system. Other outcome measures include weight, height, Cystic Fibrosis Quality of Life Questionnaire--Revised (CFQ-R), and sweat chloride. Measurements and Main Results: One hundred seventeen people with CF ages 12 and older were recruited to the study. Significant improvements were seen in LCI scores (-2.5; 95% confidence interval [CI], -3.0, 22.0) and in the percents predicted for FEV1 (8.9; 95% CI, 7.0, 10.9), FVC (6.6; 95% CI, 4.9, 8.3), and forced expiratory flow between 25% and 75% of expired volume (12.4; 95% CI, 7.8, 17.0). Overall PRAGMA-CF scores reflecting airway disease improved significantly (-3.46; 95% CI, -5.23, -1.69). Scores for trapped air, mucus plugging, and bronchial wall thickening improved significantly, but bronchiectasis scores did not. Sweat chloride levels decreased in both F508del/F508del (-43.1; 95% CI, -47.4, 238.9) and F508del/MF (-42.8; 95% CI, -48.5, -37.2) groups. Scores on the Respiratory Domain of the CFQ-R improved by 14.2 points (95% CI, 11.3, 17.2). At 1 year, sweat chloride levels were significantly lower for the F508del/F508del group compared with scores for the F508del/MF group (33.93 vs. 53.36, P,0.001). Conclusions: ETI is associated with substantial improvements in LCI2.5, spirometry, and PRAGMA-CF CT scores in people with CF ages 12 years and older. ETI led to improved nutrition and quality of life. People in the F508del/F508del group had significantly lower sweat chloride on ETI treatment compared with the F508del/MF group. [ABSTRACT FROM AUTHOR]

Lung function parameters have been used in most therapeutic studies to date. Thanks to improvements in cystic fibrosis (CF) therapy, these parameters have become a less sensitive endpoint in clinical studies. Computed tomography (CT) in CF can identify highly relevant structural lung changes, such as bronchiectasis and air trapping. CT scoring systems have been developed to quantify in a systematic fashion these structural changes on CT scans. Clinical studies have been conducted using CT scores as an outcome parameter. These studies suggest strongly that CT scoring is more sensitive than pulmonary function tests for the detection of relevant disease progression in CF. Bronchiectasis, which is progressive and irreversible in CF, is probably the most relevant structural change on CT scans that can be scored reliably. CT measurement of airway wall thickening is possible. Airway wall thickening is related to inflammation; thus, this endpoint is of significance for interventional studies that include antiinflammatory drugs.

This article presents a review and discussion of the current knowledge regarding cystic fibrosis (CF)-specific scoring of chest computed tomography (CT) scans. First, the basic principles of CT scoring systems in CF are described. Second, between- and within-observer variability of a composite CT score and of component CT scores are reviewed, and issues regarding training of CT scan readers discussed. Third, arguments regarding whether CT scoring systems are ready to be used in clinical studies as a surrogate endpoint are summarized. The between- and within-observer variability of the present CT composite scoring systems is low enough to be useful for clinical studies, although the variability for some of the component scores is larger than for others. Scoring systems fulfill the requirements for surrogate endpoints for CF lung disease, but this role could be further strengthened by including CT scans in large trials and demonstrating the correlation with true endpoints. The conclusion presented is that, given the experience of the variety of published scoring systems, it is important to develop a consensus CT scoring system for future studies in CF. Such a scoring system should evaluate all lung lobes individually and include all relevant CT findings in CF. Development of reference images for the components of this system will be important in reducing the variability between observers and to train new readers.