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BACKGROUND: Nocturnal gastro-oesophageal reflux (nGER) is common in people with respiratory diseases, but its association with pulmonary abnormalities is not known.

AIM: Investigate the association between nGER and pulmonary abnormalities on chest CT in an adult general population.

METHODS: In total, 28 846 individuals from the general population aged 50-64 years completed questionnaires and underwent chest CT, in the Swedish CArdioPulmonary BioImage Study (www.scapis.org). Participants with nGER symptoms on ≥1 night per week were defined as having nGER. Chest CT was evaluated for bronchial wall thickening, bronchiectasis, reticular abnormalities, honeycombing, cysts and ground glass opacities. Ever-smoking, current asthma, inflammatory bowel disease and autoimmune disease were defined as risk factors for pulmonary abnormalities. Analyses were adjusted for sex, age, body mass index, education level and study centre.

RESULTS: The prevalence of nGER was 9.4%. Among participants with risk factors for pulmonary abnormalities (n=4004), having nGER was positively associated with bronchial wall thickening (adjusted OR (aOR) (95% CI): 1.25 (1.07 to 1.48)) and reticular abnormalities (aOR (95% CI): 1.51 (1.04 to 2.17)), but negatively associated with cysts (aOR (95% CI): 0.68 (0.48 to 0.97)). Among participants without risk factors for CT abnormalities (n=2555), nGER did not relate with pulmonary abnormalities.

CONCLUSIONS: In a middle-aged general population, nGER was not associated with pulmonary abnormalities on chest CT. However, in the presence of other risk factors for pulmonary abnormalities, nGER was associated with bronchial wall thickening and reticular abnormalities. Persons with nGER and risk factors for pulmonary abnormalities should, therefore, be evaluated for respiratory disease and treated appropriately.

Background

Pulmonary nodules (PNs) are clinically challenging because differentiation between benign and malignant PNs is not possible at CT detection; recurring CT examinations and invasive procedures are often required in PN follow-up.

Purpose

To investigate PN prevalence in a middle-aged population and the risk factors associated with these nodules.

Materials and Methods

In this secondary analysis of the cross-sectional population-based Swedish CArdioPulmonary bioImage Study (known as SCAPIS, from November 2013 to November 2018), participants aged 50–64 years with chest CT data were analyzed. Risk factors such as smoking history, occupational exposure (vapor, dust, gas, and fumes), and lung diseases were derived from comprehensive questionnaires. Robust Poisson regression was used to evaluate associations, adjusted for age and sex, between potential risk factors and the binary outcome of nodule presence or absence. Prevalence ratios (PRs), adjusted for age and sex, and 95% CIs were estimated.

Results

Among 29 574 participants (median age, 57.4 years; IQR, 53.7–61.2 years; 15 168 women), solid nodules sized 100–300 mm³, part-solid, and ground-glass nodules were found in 1420 (4.8%), 199 (0.7%), and 430 (1.5%), respectively. The prevalence of solid nodules among participants who never, formerly, and currently smoked was 32.5% (4713 of 14 515), 34.5% (3602 of 10 437), and 37.9% (1381 of 3644), respectively. Solid nodules sized 100–300 mm³ were associated with current smoking (PR, 1.38; 95% CI: 1.19, 1.60), chronic obstructive pulmonary disease (PR, 1.72; 95% CI: 1.17, 2.53), occupational exposure (PR, 1.31; 95% CI: 1.11, 1.54), emphysema (PR, 1.56; 95% CI: 1.31, 1.86), reticulation (PR, 1.96; 95% CI: 1.47, 2.61), and bronchiectasis (PR, 2.03; 95% CI: 1.64, 2.50). In participants who had never smoked, associations were found between solid nodules at least 100 mm³ and reticulation (PR, 2.28; 95% CI: 1.55, 3.36), reported lung disease other than asthma or chronic obstructive pulmonary disease (PR, 2.26; 95% CI: 1.49, 3.43), and bronchiectasis (PR, 2.17; 95% CI: 1.60, 2.94).

Conclusion

PN prevalence was approximately the same in a middle-aged population regardless of smoking history. In participants who had never smoked, nodules were linked to reported lung disease, reticulation, and bronchiectasis.

Background: Chemoradiotherapy (CRT) is regarded as the treatment of choice for inoperable stage III non-small cell lung cancer (NSCLC) patients. Despite the curative intent, recurrence is frequent, and overall prognosis is poor. Thus, there is a need for clinical biomarkers to better predict outcome and to optimize treatment and follow-up. The aim of this study was to characterize a large cohort of real-world stage III NSCLC patients who received CRT with curative intent and to define parameters that could predict recurrence patterns, overall survival (OS) and survival time from recurrence.

Methods: This study is based on a cohort of 193 stage III NSCLC patients receiving CRT with curative intent in mid-Sweden during the years 2009–2018. Data was retrospectively collected from medical records. Clinical parameters, recurrence patterns, salvage treatment, histological and molecular data were analyzed and correlated to outcome.

Results: Median follow-up was 52 months, with a median OS of 33 months. Most patients (66%) progressed, commonly within the first 3 years following CRT. Performance status and common blood markers at recurrence were associated with worse survival. The presence of driver mutations [epidermal growth factor receptor (EGFR), Kirsten rat sarcoma viral oncogene homolog (KRAS)] or metastatic spread to N3 lymph nodes increased the risk of distant recurrence. Immunotherapy as salvage treatment was associated with a significantly better prognosis.

Conclusions: Routine diagnostic parameters can be used to predict survival and recurrence patterns in patients receiving curative CRT. Additionally, salvage treatment with immunotherapy was the strongest factor associated with longer survival after disease recurrence.

Background Non-small cell lung cancer (NSCLC) is a common neoplasm with poor prognosis in advanced stages. The clinical work-up in patients with locally advanced NSCLC mostly includes F-18-fluorodeoxyglucose positron emission tomography computed tomography (F-18-FDG PET/CT) because of its high sensitivity for malignant lesion detection; however, specificity is lower. Diverging results exist whether whole-body MRI (WB-MRI) improves the staging accuracy in advanced lung cancer. Considering WB-MRI being a more time-consuming examination compared to brain MRI, it is important to establish whether or not additional value is found in detecting and characterizing malignant lesions. The purpose of this study is to investigate the value of additional whole-body magnetic resonance imaging, instead of only brain MRI, together with F-18-FDG PET/CT in staging patients with advanced NSCLC planned for curative treatment. Material and methods In a prospective single center study, 28 patients with NSCLC stage 3 or oligometastatic disease were enrolled. In addition to F-18-FDG PET/CT, they underwent WB-MRI including the thorax, abdomen, spine, pelvis, and contrast-enhanced examination of the brain and liver. F-18-FDG PET/CT and WB-MRI were separately evaluated by two blinded readers, followed by consensus reading in which the likelihood of malignancy was assessed in detected lesions. Imaging and clinical follow-up for at least 12 months was used as reference standard. Statistical analyses included Fischer's exact test and Clopped-Pearson. Results 28 patients (mean age +/- SD 70.5 +/- 8.4 years, 19 women) were enrolled. WB-MRI and FDG-PET/CT both showed maximum sensitivity and specificity for primary tumor diagnosis and similar sensitivity (p = 1.00) and specificity (p = 0.70) for detection of distant metastases. For diagnosis of lymph node metastases, WB-MRI showed lower sensitivity, 0.65 (95% CI: 0.38-0.86) than FDG-PET/CT, 1.00 (95% CI: 0.80-1.00) (p < 0.05), but similar specificity (p = 0.59). Conclusions WB-MRI in conjunction with F-18-FDG PET/CT provides no additional value over MRI of the brain only, in staging patients with advanced NSCLC. Trial registration Registered locally and approved by the Uppsala University Hospital committee, registration number ASMR020.

Background: The effects of obesity on pulmonary gas and blood distribution in patients with acute respiratory failure remain unknown. Dual-energy computed tomography (DECT) is a X-ray-based method used to study regional distribution of gas and blood within the lung. We hypothesized that 1) regional gas/blood mismatch can be quantified by DECT; 2) obesity influences the global and regional distribution of pulmonary gas and blood; 3) regardless of ventilation modality (invasive vs. non-invasive ventilation), patients’ body mass index (BMI) has an impact on pulmonary gas/blood mismatch.

Methods: This single-centre prospective observational study enrolled 118 hypoxic COVID-19 patients (92 male) in need of respiratory support and intensive care who underwent DECT. The cohort was divided into three groups according to BMI: 1. BMI<25 kg/m² (non-obese), 2. BMI = 25–40 kg/m² (overweight to obese), and 3. BMI>40 kg/m² (morbidly obese). Gravitational analysis of Hounsfield unit distribution of gas and blood was derived from DECT and used to calculate regional gas/blood mismatch. A sensitivity analysis was performed to investigate the influence of the chosen ventilatory modality and BMI on gas/blood mismatch and adjust for other possible confounders (i.e., age and sex).

Results: 1) Regional pulmonary distribution of gas and blood and their mismatch were quantified using DECT imaging. 2) The BMI>40 kg/m² group had less hyperinflation in the non-dependent regions and more lung collapse in the dependent regions compared to the other BMI groups. In morbidly obese patients, gas and blood were more evenly distributed; therefore, the mismatch was lower than in other patients (30% vs. 36%, p < 0.05). 3) An increase in BMI of 5 kg/m² was associated with a decrease in mismatch of 3.3% (CI: 3.67% to −2.93%, p < 0.05). Neither the ventilatory modality nor age and sex affected the gas/blood mismatch (p > 0.05).

Conclusion: 1) In a hypoxic COVID-19 population needing intensive care, pulmonary gas/blood mismatch can be quantified at a global and regional level using DECT. 2) Obesity influences the global and regional distribution of gas and blood within the lung, and BMI>40 kg/m² improves pulmonary gas/blood mismatch. 3) This is true regardless of the ventilatory mode and other possible confounders, i.e., age and sex.

Trial Registration: Clinicaltrials.gov, identifier NCT04316884, NCT04474249.

Objective: The significance of the inflammatory response in the natural course of acute type B aortic dissection (ATBAD) is unknown. The aim was to characterise inflammation and its transformation over time in ATBAD using F-18-fluorodeoxyglucose (FDG) positron emission tomography (PET) with contrast enhanced magnetic resonance imaging (MRI).

Methods: Ten patients underwent FDG-PET/MRI within two weeks of ATBAD (acute phase), three to four months (subacute phase), nine to 12 months (early chronic phase), and 21 to 24 months (late chronic phase) after ATBAD. Target background ratios (TBRs) were measured in the ascending aorta, aortic arch, and descending aorta. MRI inflammatory markers were assessed in the descending aorta.

Results: Ten patients were included: median age 69 years, median clinical follow up 32 months. In the acute phase there was increased FDG uptake in the descending aorta (maximum TBR 5.8, SD [standard deviation] 1.3) compared with the ascending aorta (TBR 3.3, SD 0.8, p < .010) and arch (TBR 4.2, SD 0.6, p = .010). The maximum TBR of the descending aorta decreased from the acute to subacute phase (TBR 3.5, SD 0.6, p = .010) and further to the early chronic phase (TBR 2.9, SD 0.4, p = .030) but was stable thereafter. The acute phase maximum TBR in the ascending aorta (TBR 3.3) and arch (TBR 4.2) decreased to the subacute phase (ascending: TBR 2.8, SD 0.6, p = .020; arch: TBR 2.7, SD 0.4, p = .010) and was stable thereafter. Four patients underwent surgical aortic repair (three for aortic dilatation at one, five, and 28 months and one for visceral ischaemia at three weeks). MRI signs of inflammation were present in all surgically treated patients vs. two of six of medically treated patients (p= .048).

Conclusion: ATBAD is associated with increased FDG uptake in the acute phase primarily in the descending aorta, but also involving the aortic arch and ascending aorta, indicating an inflammatory response in the whole aorta. Inflammation subsides early in the ascending aorta and arch (three months), whereas it stabilised later in the descending aorta (nine to 12 months). MRI signs of inflammation were more frequent in patients who later needed surgical treatment and merit further investigation.

Background: Steroids have been shown to reduce inflammation, hypoxic pulmonary vasoconstriction (HPV) and lung edema. Based on evidence from clinical trials, steroids are widely used in severe COVID-19. However, the effects of steroids on pulmonary gas volume and blood volume in this group of patients are unexplored.

Objective: Profiting by dual-energy computed tomography (DECT), we investigated the relationship between the use of steroids in COVID-19 and distribution of blood volume as an index of impaired HPV. We also investigated whether the use of steroids influences lung weight, as index of lung edema, and how it affects gas distribution.

Methods: Severe COVID-19 patients included in a single-center prospective observational study at the intensive care unit at Uppsala University Hospital who had undergone DECT were enrolled in the current study. Patients' cohort was divided into two groups depending on the administration of steroids. From each patient's DECT, 20 gas volume maps and the corresponding 20 blood volume maps, evenly distributed along the cranial-caudal axis, were analyzed. As a proxy for HPV, pulmonary blood volume distribution was analyzed in both the whole lung and the hypoinflated areas. Total lung weight, index of lung edema, was estimated.

Results: Sixty patients were analyzed, whereof 43 received steroids. Patients not exposed to steroids showed a more extensive non-perfused area (19% vs 13%, p < 0.01) and less homogeneous pulmonary blood volume of hypoinflated areas (kurtosis: 1.91 vs 2.69, p < 0.01), suggesting a preserved HPV compared to patients treated with steroids. Moreover, patients exposed to steroids showed a significantly lower lung weight (953 gr vs 1140 gr, p = 0.01). A reduction in alveolar-arterial difference of oxygen followed the treatment with steroids (322 +/- 106 mmHg at admission vs 267 +/- 99 mmHg at DECT, p = 0.04).

Conclusions The use of steroids might cause impaired HPV and might reduce lung edema in severe COVID-19. This is consistent with previous findings in other diseases. Moreover, a reduced lung weight, as index of decreased lung edema, and a more homogeneous distribution of gas within the lung were shown in patients treated with steroids. Trial registration: Clinical Trials ID: NCT04316884, Registered March 13, 2020.

Background

Ground glass opacity (GGO) is the main HRCT feature representing alveolitis in systemic sclerosis-associated interstitial lung disease (SSc-ILD), but may also represent other conditions such as atelectasis or edema. It is unclear how much this is affected by the HRCT scan protocol used. We aimed to compare the performance of three different HRCT protocols to evaluate the degree of SSc-ILD related changes.

Methods

Eleven patients with SSc underwent chest HRCT scan by three different protocols: First, a supine scan after lying down for 15 minutes, then two scans in alternating order: A prone position scan, and a supine position scan after performing 10 deep breaths using a positive expiratory pressure (PEP) device. The HRCT scans were evaluated by the Warrick score system for ILD-related findings.

Results

The three HRCT protocols were compared and resulted in different mean (95% CI) Warrick scores: 9.4 (5.3–13.4) in supine after rest; 7.5 (95% CI 3.8–11.1) in prone and 7.6 (95% CI 4.2–11.1) in supine after PEP. When comparing supine after rest to prone and supine after PEP, the latter two scans had a significantly lower score (p = 0.001 for both comparisons). In all cases, only sub-scores for ground glass opacities differed, while sub-scores for fibrosis-related changes did not change.

Conclusions

Different HRCT scan protocols significantly altered the Warrick severity score for SSc-ILD findings, primarily because of changes in ground glass opacities. These differences may be clinically meaningful.

BackgroundTypical features differentiate COVID-19-associated lung injury from acute respiratory distress syndrome. The clinical role of chest computed tomography (CT) in describing the progression of COVID-19-associated lung injury remains to be clarified. We investigated in COVID-19 patients the regional distribution of lung injury and the influence of clinical and laboratory features on its progression.MethodsThis was a prospective study. For each CT, twenty images, evenly spaced along the cranio-caudal axis, were selected. For regional analysis, each CT image was divided into three concentric subpleural regions of interest and four quadrants. Hyper-, normally, hypo- and non-inflated lung compartments were defined. Nonparametric tests were used for hypothesis testing (alpha =0.05). Spearman correlation test was used to detect correlations between lung compartments and clinical features.ResultsTwenty-three out of 111 recruited patients were eligible for further analysis. Five hundred-sixty CT images were analyzed. Lung injury, composed by hypo- and non-inflated areas, was significantly more represented in subpleural than in core lung regions. A secondary, centripetal spread of lung injury was associated with exposure to mechanical ventilation (p<0.04), longer spontaneous breathing (more than 14 days, p<0.05) and non-protective tidal volume (p<0.04). Positive fluid balance (p<0.01), high plasma D-dimers (p<0.01) and ferritin (p<0.04) were associated with increased lung injury.ConclusionsIn a cohort of COVID-19 patients with severe respiratory failure, a predominant subpleural distribution of lung injury is observed. Prolonged spontaneous breathing and high tidal volumes, both causes of patient self-induced lung injury, are associated to an extensive involvement of more central regions. Positive fluid balance, inflammation and thrombosis are associated with lung injury.Trial registration Study registered a priori the 20th of March, 2020. Clinical Trials ID NCT04316884.