The diagnostic trajectories of Danish patients with autoimmune rheumatologic disease associated interstitial lung disease: an interview-based study.

Background: Autoimmune rheumatologic disease associated interstitial lung diseases (ARD-ILD) are rare conditions and the association between ARDs and respiratory symptoms often goes unrecognised by ARD patients and general practitioners (GPs). The diagnostic trajectory from the first respiratory symptoms to an ARD-ILD diagnosis is often delayed and may increase the burden of symptoms and allow further disease progression.The aim of this study was to 1) characterise the diagnostic trajectories of ARD-ILD patients and to 2) identify barriers for obtaining a timely ILD diagnosis based on the experiences and perceptions of both patients and healthcare professionals. Method: Semi-structured qualitative interviews were conducted with Danish ARD-ILD patients, rheumatologists, pulmonologists and ILD nurses. Results: Sixteen patients, six rheumatologists, three ILD nurses and three pulmonologists participated. Five characteristics of diagnostic trajectories were identified in the patient interviews: 1) early referral to lung specialists; 2) early delay; 3) delay or shortcut depending on specific circumstances; 4) parallel diagnostic trajectories connected late in the process; 5) early identification of lung involvement without proper interpretation. With the exception of early referral to lung specialists, all of the diagnostic trajectory characteristics identified led to delayed diagnosis. Delayed diagnostic trajectories resulted in patients experiencing increased uncertainty. Inconsistent disease terminology, insufficient knowledge and lack of awareness of ARD-ILD among central healthcare professionals and delayed referral to ILD specialists were main contributors to the diagnostic delay identified by the informants. Conclusion: Five characteristics of the diagnostic trajectories were identified, four of which led to diagnostic delay of ARD-ILD. Improved diagnostic trajectories can shorten the diagnostic trajectory and increase early access to appropriate specialist medical care. Improved awareness and expertise in ARD-ILD across different medical specialties, especially among GPs, may contribute to more efficient and timely diagnostic trajectories and improved patient experiences.

Turnover of type I and III collagen predicts progression of idiopathic pulmonary fibrosis.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is characterized by the accumulation of fibrillar collagens in the alveolar space resulting in reduced pulmonary function and a high mortality rate. Biomarkers measuring the turnover of type I and III collagen could provide valuable information for prognosis and treatment decisions in IPF. METHODS: Serological biomarkers reflecting the formation of type III collagen (PRO-C3) and degradation of type I (C1M) and III collagen (C3M) were evaluated in a real-world cohort of 178 newly diagnosed IPF patients. Blood samples and clinical data were collected at baseline, six, and 12 months. Baseline and longitudinal biomarker levels were related to disease progression of IPF (defined as ≥ 5% decline in forced vital capacity (FVC) and/or ≥ 10% decline in diffusing capacity for carbon monoxide (DLco) and/or all-cause mortality at 12 months). Furthermore, we analysed differences in percentage change of biomarker levels from baseline between patients receiving antifibrotic treatment or not. RESULTS: Increased baseline levels of type I and III collagen turnover biomarkers were associated with a greater risk of disease progression within 12 months compared to patients with a low baseline type I and III collagen turnover. Patients with progressive disease had higher serum levels of C1M (P = 0.038) and PRO-C3 (P = 0.0022) compared to those with stable disease over one year. There were no differences in biomarker levels between patients receiving pirfenidone, nintedanib, or no antifibrotics. CONCLUSION: Baseline levels of type I and III collagen turnover were associated with disease progression within 12 months in a real-world cohort of IPF patients. Longitudinal biomarker levels of type I and III collagen turnover were related to progressive disease. Moreover, antifibrotic therapy did not affect type I and III collagen turnover biomarkers in these patients. PRO-C3 and C1M may be potential biomarkers for a progressive disease behavior in IPF.

Lung nodule volumetry: segmentation algorithms within the same software package cannot be used interchangeably.

OBJECTIVE: We examined the reproducibility of lung nodule volumetry software that offers three different volumetry algorithms. METHODS: In a lung cancer screening trial, 188 baseline nodules >5 mm were identified. Including follow-ups, these nodules formed a study-set of 545 nodules. Nodules were independently double read by two readers using commercially available volumetry software. The software offers readers three different analysing algorithms. We compared the inter-observer variability of nodule volumetry when the readers used the same and different algorithms. RESULTS: Both readers were able to correctly segment and measure 72% of nodules. In 80% of these cases, the readers chose the same algorithm. When readers used the same algorithm, exactly the same volume was measured in 50% of readings and a difference of >25% was observed in 4%. When the readers used different algorithms, 83% of measurements showed a difference of >25%. CONCLUSION: Modern volumetric software failed to correctly segment a high number of screen detected nodules. While choosing a different algorithm can yield better segmentation of a lung nodule, reproducibility of volumetric measurements deteriorates substantially when different algorithms were used. It is crucial even in the same software package to choose identical parameters for follow-up.

Exploring the role of CT densitometry: a randomised study of augmentation therapy in alpha1-antitrypsin deficiency.

Assessment of emphysema-modifying therapy is difficult, but newer outcome measures offer advantages over traditional methods. The EXAcerbations and Computed Tomography scan as Lung End-points (EXACTLE) trial explored the use of computed tomography (CT) densitometry and exacerbations for the assessment of the therapeutic effect of augmentation therapy in subjects with alpha(1)-antitrypsin (alpha(1)-AT) deficiency. In total, 77 subjects (protease inhibitor type Z) were randomised to weekly infusions of 60 mg x kg(-1) human alpha(1)-AT (Prolastin) or placebo for 2-2.5 yrs. The primary end-point was change in CT lung density, and an exploratory approach was adopted to identify optimal methodology, including two methods of adjustment for lung volume variability and two statistical approaches. Other end-points were exacerbations, health status and physiological indices. CT was more sensitive than other measures of emphysema progression, and the changes in CT and forced expiratory volume in 1 s were correlated. All methods of densitometric analysis concordantly showed a trend suggestive of treatment benefit (p-values for Prolastin versus placebo ranged 0.049-0.084). Exacerbation frequency was unaltered by treatment, but a reduction in exacerbation severity was observed. In patients with alpha(1)-AT deficiency, CT is a more sensitive outcome measure of emphysema-modifying therapy than physiology and health status, and demonstrates a trend of treatment benefit from alpha(1)-AT augmentation.

Quantitative assessment of regional emphysema distribution in patients with chronic obstructive pulmonary disease (COPD).

PURPOSE: To compare objective and subjective assessment of the distribution of emphysema in unselected patients with chronic obstructive pulmonary disease (COPD). MATERIAL AND METHODS: 167 patients were computed tomography (CT) scanned, and the relative area (RA-910) of emphysema in each CT slice was plotted against table position. The craniocaudal distribution was calculated as the slope of the regression line, and grouped as upper-lung-zone predominance (ULP), lower-lung-zone predominance (LLP), or mild/homogeneous distribution (MHE). CT scans were also classified as ULP, LLP, and MHE based on visual assessment of three high-resolution CT (HRCT) slices, and the leading pattern of emphysema was classified as centrilobular (CLE), paraseptal (PSE), panlobular (PLE), or no emphysema (NE). RESULTS: By objective classification, scans were divided into almost equal numbers of ULP, LLP, and MHE, whereas visual evaluation classified more scans as ULP (P<0.001) and very few as LLP (P<0.0001). In patients with CLE, 49% had ULP by objective classification, whereas LLP was the commonest leading pattern in PSE, PLE, and NE. CONCLUSION: We found significant discrepancies between the objective and subjective distributions of emphysema in various morphological patterns, which may be of clinical importance in, for instance, lung-volume-reduction surgery.

Quantitative computed tomography and aerosol morphometry in COPD and alpha1-antitrypsin deficiency.

Relative area of emphysema below -910 Hounsfield units (RA-910) and 15th percentile density (PD15) are quantitative computed tomography (CT) parameters used in the diagnosis of emphysema. New concepts for noninvasive diagnosis of emphysema are aerosol-derived airway morphometry, which measures effective airspace dimensions (EAD) and aerosol bolus dispersion (ABD). Quantitative CT, ABD and EAD were compared in 20 smokers with chronic obstructive pulmonary disease (COPD) and 22 patients with alpha1-antitrypsin deficiency (AAD) with a similar degree of airway obstruction and reduced diffusion capacity. In both groups, there was a significant correlation between RA-910 and PD15 and pulmonary function tests (PFTs). A significant correlation was also found between EAD, RA-910 and PD15 in the study population as a whole. Upon separation into two groups, the significance disappeared for the smokers with COPD and strengthened for those with AAD, where EAD correlated significantly with RA-910 and PD15. ABD was similar in the two groups and did not correlate with PFT and quantitative CT in either group. In conclusion, based on quantitative computed tomography and aerosol-derived airway morphometry, emphysema was significantly more severe in patients with alpha1-antitrypsin deficiency compared with patients with usual emphysema, despite similar measures of pulmonary function tests.

Alpha1-antitrypsin deficiency. 7: Computed tomographic imaging in alpha1-antitrypsin deficiency.

Computed tomographic scanning may replace lung function tests as the golden standard for assessing the response to known and novel treatments for alpha1-antitrypsin deficiency.

Short-term reproducibility of computed tomography-based lung density measurements in alpha-1 antitrypsin deficiency and smokers with emphysema.

PURPOSE: To study the short-term reproducibility of lung density measurements by multi-slice computed tomography (CT) using three different radiation doses and three reconstruction algorithms. MATERIAL AND METHODS: Twenty-five patients with smoker's emphysema and 25 patients with alpha1-antitrypsin deficiency underwent 3 scans at 2-week intervals. Low-dose protocol was applied, and images were reconstructed with bone, detail, and soft algorithms. Total lung volume (TLV), 15th percentile density (PD-15), and relative area at -910 Hounsfield units (RA-910) were obtained from the images using Pulmo-CMS software. Reproducibility of PD-15 and RA-910 and the influence of radiation dose, reconstruction algorithm, and type of emphysema were then analysed. RESULTS: The overall coefficient of variation of volume adjusted PD-15 for all combinations of radiation dose and reconstruction algorithm was 3.7%. The overall standard deviation of volume-adjusted RA-910 was 1.7% (corresponding to a coefficient of variation of 6.8%). Radiation dose, reconstruction algorithm, and type of emphysema had no significant influence on the reproducibility of PD-15 and RA-910. However, bone algorithm and very low radiation dose result in overestimation of the extent of emphysema. CONCLUSION: Lung density measurement by CT is a sensitive marker for quantitating both subtypes of emphysema. A CT-protocol with radiation dose down to 16 mAs and soft or detail reconstruction algorithm is recommended.

Volume adjustment of lung density by computed tomography scans in patients with emphysema.

PURPOSE: To determine how to adjust lung density measurements for the volume of the lung calculated from computed tomography (CT) scans in patients with emphysema. MATERIAL AND METHODS: Fifty patients with emphysema underwent 3 CT scans at 2-week intervals. The scans were analyzed with a software package that detected the lung in contiguous images and subsequently generated a histogram of the pixel attenuation values. The total lung volume (TLV), lung weight, percentile density (PD), and relative area of emphysema (RA) were calculated from this histogram. RA and PD are commonly applied measures of pulmonary emphysema derived from CT scans. These parameters are markedly influenced by changes in the level of inspiration. The variability of lung density due to within-subject variation in TLV was explored by plotting TLV against PD and RA. RESULTS: The coefficients for volume adjustment for PD were relatively stable over a wide range from the 10th to the 80th percentile, whereas for RA the coefficients showed large variability especially in the lower range, which is the most relevant for quantitation of pulmonary emphysema. CONCLUSION: Volume adjustment is mandatory in repeated CT densitometry and is more robust for PD than for RA. Therefore, PD seems more suitable for monitoring the progression of emphysema.