Review on radiological evolution of COVID-19 pneumonia using computed tomography.

BACKGROUND: Pneumonia is the main manifestation of coronavirus disease 2019 (COVID-19) infection. Chest computed tomography is recommended for the initial evaluation of the disease; this technique can also be helpful to monitor the disease progression and evaluate the therapeutic efficacy. AIM: To review the currently available literature regarding the radiological follow-up of COVID-19-related lung alterations using the computed tomography scan, to describe the evidence about the dynamic evolution of COVID-19 pneumonia and verify the potential usefulness of the radiological follow-up. METHODS: We used pertinent keywords on PubMed to select relevant studies; the articles we considered were published until October 30, 2020. Through this selection, 69 studies were identified, and 16 were finally included in the review. RESULTS: Summarizing the included works' findings, we identified well-defined stages in the short follow-up time frame. A radiographic deterioration reaching a peak roughly within the first 2 wk; after the peak, an absorption process and repairing signs are observed. At later radiological follow-up, with the limitation of little evidence available, the lesions usually did not recover completely. CONCLUSION: Following computed tomography scan evolution over time could help physicians better understand the clinical impact of COVID-19 pneumonia and manage the possible sequelae; a longer follow-up is advisable to verify the complete resolution or the presence of long-term damage.

Cryptogenic Fibrosing Pleuritis.

We report the case of a 46-year-old male patient who was referred for chest pain and bilateral pleural effusion. Despite treatment with antibiotics and steroids, the pleural effusion worsened over a few months until pulmonary function was halved. The CT scan showed bilateral pleural thickening with right basal opacity. Histology revealed extensive fibrotic tissue with focal collections of lymphocytes and giant cells without traces of asbestos bodies. Since no evidence of an infectious, embolic or occupational aetiology was found, this bilateral pleural effusion progressing to diffuse pleural thickening was diagnosed as cryptogenic fibrosing pleuritis, a rare pleural disease. LEARNING POINTS: Bilateral pleural effusion progressing to diffuse pleural thickening was diagnosed as cryptogenic fibrosing pleuritis, a rare pleural disease.Cryptogenic fibrosing pleuritis was treated with high-dose corticosteroids.The patient showed stable disease at 6-year follow-up.

Ventilation Heterogeneity in Asthma and COPD: The Value of the Poorly Communicating Fraction as the Ratio of Total Lung Capacity to Alveolar Volume.

BACKGROUND: The ventilation heterogeneity (VH) is reliably assessed by the multiple-breath nitrogen washout (MBNW), which provides indices of conductive (Scond) and acinar (Sacin) VH as well as the lung clearance index (LCI), an index of global VH. VH can be alternatively measured by the poorly communicating fraction (PCF), that is, the ratio of total lung capacity by body plethysmography to alveolar volume from the single-breath lung diffusing capacity measurement. OBJECTIVES: Our objective was to assess VH by PCF and MBNW in patients with asthma and with COPD and to compare PCF and MBNW parameters in both patient groups. METHOD: We studied 35 asthmatic patients and 45 patients with COPD. Each patient performed spirometry, body plethysmography, diffusing capacity, and MBNW test. RESULTS: Compared to COPD patients, asthmatics showed a significantly lesser degree of airflow obstruction and lung hyperinflation. In asthmatic patients, both PCF and LCI and Sacin values were significantly lower than the corresponding ones of COPD patients. In addition, in both patient groups, PCF showed a positive correlation with LCI (p < 0.05) and Sacin (p < 0.05), but not with Scond. Lastly, COPD patients with PCF >30% were highly likely to have a value ≥2 of the mMRC dyspnea scale. CONCLUSIONS: These results showed that PCF, a readily measure derived from routine pulmonary function testing, can provide a comprehensive measure of both global and acinar VH in asthma and in COPD patients and can be considered as a comparable tool to the well-established MBNW technique.

Serum markers of pulmonary epithelial damage in systemic sclerosis-associated interstitial lung disease and disease progression.

BACKGROUND AND OBJECTIVE: The course of systemic sclerosis-associated interstitial lung disease (SSc-ILD) is highly variable, and accurate prognostic markers are needed. KL-6 is a mucin-like glycoprotein (MUC1) expressed by type II pneumocytes, while CYFRA 21-1 is expressed by alveolar and bronchiolar epithelial cells. Both are released into the blood from cell injury. METHODS: Serum KL-6 and CYFRA 21-1 levels were measured in a retrospective (n = 189) and a prospective (n = 118) cohort of SSc patients. Genotyping of MUC1 rs4072037 was performed. Linear mixed-effect models were used to evaluate the relationship with change in lung function parameters over time, while association with survival was evaluated with Cox proportional hazard analysis. RESULTS: In both cohorts, KL-6 and CYFRA 21-1 were highest in patients with lung involvement, and in patients with extensive rather than limited ILD. KL-6 was higher in patients carrying the MUC1 rs4072037 G allele in both cohorts. In patients with SSc-ILD, serum KL-6, but not CYFRA 21-1, was significantly associated with DLCO decline in both cohorts (P = 0.001 and P = 0.004, respectively), and with FVC decline in the retrospective cohort (P = 0.005), but not the prospective cohort. When combining the cohorts and subgrouping by severity (median CPI = 45.97), KL-6 remained predictive of decline in DLCO in both milder (P = 0.007) and more severe disease (P = 0.02) on multivariable analysis correcting for age, gender, ethnicity, smoking history and MUC1 allele carriage. CONCLUSION: Our results suggest serum KL-6 predicts decline in lung function in SSc, suggesting its clinical utility in risk stratification for progressive SSc-ILD.

Systemic thromboembolism from a misdiagnosed non-bacterial thrombotic endocarditis in a patient with lung cancer: A case report.

Thromboembolic events are frequent in patients with cancer, commonly involving the venous and pulmonary circulation. The arterial system is rarely implicated in embolism and, when involved, a cardiogenic origin should always be excluded. In the present study, a case of a patient who developed multiple embolic events concomitantly with the diagnosis of locally-advanced non-small cell lung cancer with high expression levels of programmed death-ligand 1 (PD-L1) in >50% of tumor cells is reported. A cardiac defect interpreted as a patent foramen ovale required low molecular weight heparin administration. Despite the anti-coagulant therapy, before first-line anticancer treatment with pembrolizumab immunotherapy could be administered due to high PD-L1 expression levels, a new hospitalization was required due to the onset of novel ischemic manifestation. New transthoracic and transesophageal echocardiography revealed a previously misdiagnosed vegetation of the mitral valve that caused systemic embolization. The lack of any sign of infection led to the diagnosis of a non-bacterial thrombotic endocarditis (NBTE), whose embolic sprouting gave rise to the widespread ischemic events. No active anticancer treatment was feasible due to the rapid progression of the disease. NBTE can evolve quickly, eventually preventing any chance of treatment targeting the primary cause, which in the present study was lung cancer. If NBTE can be correctly diagnosed sooner then there may be the potential for anticancer therapy that does not worsen the hypercoagulability state, thus improving cancer-associated survival.

A pulmonary infection by Actinomyces odontolyticus and Veillonella atypica in an immunocompetent patient with dental caries.

Actinomycosis is a rare, chronic granulomatous infection, frequently associated with immunocompromised states, but it can also affect healthy people. Here, we report a case of a pulmonary infection by Actinomyces odontolitycus and Veillonella atypica due to a dental caries in an immunocompetent 65-year-old man patient.

Overall mortality in combined pulmonary fibrosis and emphysema related to systemic sclerosis.

Objectives: This multicentre study aimed to investigate the overall mortality of combined pulmonary fibrosis and emphysema (CPFE) in systemic sclerosis (SSc) and to compare CPFE-SSc characteristics with those of other SSc subtypes (with interstitial lung disease-ILD, emphysema or neither). Methods: Chest CTs, anamnestic data, immunological profile and pulmonary function tests of patients with SSc were retrospectively collected. Each chest CT underwent a semiquantitative assessment blindly performed by three radiologists. Patients were clustered in four groups: SSc-CPFE, SSc-ILD, SSc-emphysema and other-SSc (without ILD nor emphysema). The overall mortality of these groups was calculated by Kaplan-Meier method and compared with the stratified log-rank test; Kruskal-Wallis test, t-Student test and χ² test assessed the differences between groups. P<0.05 was considered statistically significant. Results: We enrolled 470 patients (1959 patient-year); 15.5 % (73/470) died during the follow-up. Compared with the SSc-ILD and other-SSc, in SSc-CPFE there was a higher prevalence of males, lower anticentromere antibodies prevalence and a more reduced pulmonary function (p<0.05). The Kaplan-Meier survival analysis demonstrates a significantly worse survival in patients with SSc-CPFE (HR vs SSc-ILD, vs SSc-emphysema and vs other-SSc, respectively 1.6 (CI 0.5 to 5.2), 1.6 (CI 0.7 to 3.8) and 2.8 (CI 1.2 to 6.6). Conclusions: CPFE increases the mortality risk in SSc along with a highly impaired lung function. These findings strengthen the importance to take into account emphysema in patients with SSc with ILD.

Research highlights from the 2018 ERS International Congress: interstitial lung diseases.

This article reviews a selection of the scientific presentations on interstitial lung disease (ILD)/diffuse parenchymal lung disease (DPLD) that were made at the 2018 European Respiratory Society (ERS) International Congress in Paris. A number of advances in the epidemiology, pathogenesis, diagnosis and treatment of these disorders were presented and discussed by clinicians and researchers. The research topics span over all four groups of ERS Assembly 12: Interstitial Lung Diseases (Group 12.01: Idiopathic interstitial pneumonias; Group 12.02: ILD/DPLD of known origin; Group 12.03: Sarcoidosis and other granulomatous ILD/DPLD; Group 12.04: Rare ILD/DPLD).

A High Degree of Dyspnea Is Associated With Poor Maximum Exercise Capacity in Subjects With COPD With the Same Severity of Air-Flow Obstruction.

BACKGROUND: In patients with COPD, limited data have been reported concerning the association between dyspnea perception and exercise tests. Moreover, the perception of dyspnea has not been analyzed in patients with the same severity of air-flow obstruction. The aim of our study was to evaluate the relationship between the degree of dyspnea and exercise capacity in subjects with COPD who had the same severity of air-flow obstruction. METHODS: We assessed dyspnea perception and maximum exercise capacity by using the modified Medical Research Council dyspnea scale (mMRC) questionnaire and by using the symptom-limited incremental cardiopulmonary exercise test, respectively. A propensity score matching was used to obtain the balance between the subjects with COPD and with an mMRC questionnaire score <2 and ≥2 (mMRC score) according to the severity of air-flow obstruction. RESULTS: A total of 249 ambulatory adult patients with stable COPD (mean age, 68 y) were considered in the full cohort. After propensity score analysis, 160 subjects (65% men; mean ± SD FEV1, 47.5 ± 12.8% of predicted) were included in our study cohort. The subjects with an mMRC questionnaire score ≥2 in comparison with those with an mMRC questionnaire score <2 showed lower values in oxygen uptake at peak (VO2 max) (P = .002) and in maximum work load (P < .001). In the regression models, the mMRC questionnaire score was able to predict oxygen uptake at peak (P < .001) and at maximum work load (P < .001). CONCLUSIONS: In subjects with COPD and with the same severity of air-flow obstruction, a high score in dyspnea was related to a poor maximum exercise capacity. Our results support the view that, in COPD, the severity of air-flow obstruction was less informative than symptoms in the combined assessment of the disease.

Effect of ambulatory oxygen on quality of life for patients with fibrotic lung disease (AmbOx): a prospective, open-label, mixed-method, crossover randomised controlled trial.

BACKGROUND: In fibrotic interstitial lung diseases, exertional breathlessness is strongly linked to health-related quality of life (HRQOL). Breathlessness is often associated with oxygen desaturation, but few data about the use of ambulatory oxygen in patients with fibrotic interstitial lung disease are available. We aimed to assess the effects of ambulatory oxygen on HRQOL in patients with interstitial lung disease with isolated exertional hypoxia. METHODS: AmbOx was a prospective, open-label, mixed-method, crossover randomised controlled clinical trial done at three centres for interstitial lung disease in the UK. Eligible patients were aged 18 years or older, had fibrotic interstitial lung disease, were not hypoxic at rest but had a fall in transcutaneous arterial oxygen saturation to 88% or less on a screening visit 6-min walk test (6MWT), and had self-reported stable respiratory symptoms in the previous 2 weeks. Participants were randomly assigned (1:1) to either oxygen treatment or no oxygen treatment for 2 weeks, followed by crossover for another 2 weeks. Randomisation was by a computer-generated sequence of treatments randomly permuted in blocks of constant size (fixed size of ten). The primary outcome, which was assessed by intention to treat, was the change in total score on the King's Brief Interstitial Lung Disease questionnaire (K-BILD) after 2 weeks on oxygen compared with 2 weeks of no treatment. General linear models with treatment sequence as a fixed effect were used for analysis. Patient views were explored through semi-structured topic-guided interviews in a subgroup of participants. This study was registered with ClinicalTrials.gov, number NCT02286063, and is closed to new participants with all follow-up completed. FINDINGS: Between Sept 10, 2014, and Oct 5, 2016, 84 patients were randomly assigned, 41 randomised to ambulatory oxygen first and 43 to no oxygen. 76 participants completed the trial. Compared with no oxygen, ambulatory oxygen was associated with significant improvements in total K-BILD scores (mean 55·5 [SD 13·8] on oxygen vs 51·8 [13·6] on no oxygen, mean difference adjusted for order of treatment 3·7 [95% CI 1·8 to 5·6]; p<0·0001), and scores in breathlessness and activity (mean difference 8·6 [95% CI 4·7 to 12·5]; p<0·0001) and chest symptoms (7·6 [1·9 to 13·2]; p=0·009) subdomains. However, the effect on the psychological subdomain was not significant (2·4 [-0·6 to 5·5]; p=0·12). The most common adverse events were upper respiratory tract infections (three in the oxygen group and one in the no-treatment group). Five serious adverse events, including two deaths (one in each group) occurred, but none were considered to be related to treatment. INTERPRETATION: Ambulatory oxygen seemed to be associated with improved HRQOL in patients with interstitial lung disease with isolated exertional hypoxia and could be an effective intervention in this patient group, who have few therapeutic options. However, further studies are needed to confirm this finding. FUNDING: UK National Institute for Health Research.

Heart rate recovery is associated with ventilatory constraints and excess ventilation during exercise in patients with chronic obstructive pulmonary disease.

Background Heart rate recovery delay is a marker of cardiac autonomic dysfunction. In chronic obstructive pulmonary disease patients, the ventilatory response to exercise during incremental cardiopulmonary exercise test may add information about dynamic hyperinflation by low values of inspiratory capacity/total lung capacity ratio (at peak) and excess ventilation by the slope of minute ventilation to carbon dioxide output ratio (VE/VCO2 slope). We aimed to assess if the ventilatory response to exercise might be a determinant for heart rate recovery delay. Design An observational, prospective study. Methods Anthropometric characteristics, lung function and cardiopulmonary exercise test data were recorded in chronic obstructive pulmonary disease outpatients. A cut-off of heart rate recovery of 12 or more beats was used to define heart rate recovery delay. Results Of 254 patients enrolled, 156 (61%) showed heart rate recovery delay. As compared to patients with normal heart rate recovery, patients with delay were older, with a worse lung function and with lower values of peak oxygen uptake, maximal workload, oxygen pulse at rest and at peak, and inspiratory capacity/total lung capacity at peak. Conversely, VE/VCO2 slope and dyspnoea and leg fatigue perception at peak were higher in patients with heart rate recovery delay. In the multivariate regression model adjusted for age, sex, fat-free mass, heart rate at rest and use of ß-blockers, we found that inspiratory capacity/total lung capacity at peak (<0.25) (odds ratio 2.61; P = 0.007) and VE/VCO2 slope (>32) (odds ratio 2.26; P = 0.018) predict the risk of heart rate recovery delay. Conclusions In chronic obstructive pulmonary disease outpatients, heart rate recovery is associated with dynamic hyperinflation and excess ventilation during exercise.

Spot the trachea! A wide paratracheal air cyst of not easy definition.

We report a case of a 68-year-old woman with an occasional image of a wide paratracheal oval air cyst of not easy definition. Patient had never received a chest X-ray and she had never suffered from symptoms that needed to investigate the trachea or the neck. The diagnostic hypothesis was a wide tracheal diverticulum or a bronchogenic cyst.

Next generation beta adrenoreceptor agonists for the treatment of asthma.

INTRODUCTION: A fixed-dose inhalation of a long-acting ß-agonist (LABA) and inhaled corticosteroids (ICS) is commonly recommended for moderate to severe asthmatic patients not adequately controlled by an ICS only. In order to improve the patients' adherence and the control of disease there is a noteworthy interest for the next generation inhaled ß adrenoreceptor agonists maintaining an over 24 hours bronchodilatation and used once-daily (ultra-LABAs). This review focuses on the currently available evidences on the clinical role of any single ultra-LABAs in the treatment of asthmatic patients. Areas covered: New ultra-LABAs have been developed in recent years for the treatment of asthma. In particular, several evidences in asthmatic patients include indacaterol, vilanterol, olodaterol, and abediterol. Expert opinion: Pharmacologically, all new ultra-LABAs considered have demonstrated a good ability to maintain a true bronchodilatation for over 24 hours and a good safety profile. This aspect could be a key point to improve the patient's perspective, the adherence to the treatment regimens and therefore the control of disease. At this time, however, limited data are available and no ultra-LABA+ICS may be recommended as preferred.

Quantitative chest computed tomography is associated with two prediction models of mortality in interstitial lung disease related to systemic sclerosis.

Objective: In this multicentre study, we aimed to evaluate the capacity of a computer-assisted automated QCT method to identify patients with SSc-associated interstitial lung disease (SSc-ILD) with high mortality risk according to validated composite clinical indexes (ILD-Gender, Age, Physiology index and du Bois index). Methods: Chest CT, anamnestic data and pulmonary function tests of 146 patients with SSc were retrospectively collected, and the ILD-Gender, Age, Physiology score and DuBois index were calculated. Each chest CT underwent an operator-independent quantitative assessment performed with a free medical image viewer (Horos). The correlation between clinical prediction models and QCT parameters was tested. A value of P < 0.05 was considered statistically significant. Results: Most QCT parameters had a statistically different distribution in patients with diverging mortality risk according to both clinical prediction models (P < 0.01). The cut-offs of QCT parameters were calculated by receiver operating characteristic curve analysis, and most of them could discriminate patients with different mortality risk according to clinical prediction models. Conclusion: QCT assessment of SSc-ILD can discriminate between well-defined different mortality risk categories, supporting its prognostic value. These findings, together with the operator independence, strengthen the validity and clinical usefulness of QCT for assessment of SSc-ILD.

Quantitative CT indexes are significantly associated with exercise oxygen desaturation in interstitial lung disease related to systemic sclerosis.

INTRODUCTION: Interstitial Lung Disease (ILD) is the first cause of death related to Systemic Sclerosis (SSc). The ILD severity can be assessed with clinical, functional and radiological outcome. Nevertheless none of them is completely validated in clinical practice. Recently a new radiological evaluation based on Quantitative Computed Tomography Indexes (QCTI) was proposed on the basis of voxel-wise quantitative analysis of chest CT. OBJECTIVES: The main aim of this study is to verify if QCTI can identify SSc patients with significant oxygen desaturation during the 6 min walking test. The discrimination performance of QCTI and the other clinical, functional and radiological outcomes was also investigated. METHODS: Sixty three SSc patients were enrolled and underwent clinical, functional and radiological assessment. Inspiratory chest CT of each patient was evaluated with both a visual score and a dedicated software for segmentation of the lung in order to obtained QCTI. RESULTS: Patients with or without severe oxygen desaturation showed different QCTI, CT visual score and functional outcomes (P < 0.05). In particular, QCTI and functional outcomes showed almost the same discriminating ability. CONCLUSION: QCTI detect SSc patients with a severe oxygen desaturation after exercise as well as functional and other radiological outcomes. It is remarkable that QCTI are the only outcome without intra- or inter-reader variability because they are obtained with an algorithm. These findings bring out the QCTI as a concrete tool in SSc-ILD assessment.

Relationships between emphysema and airways metrics at High-Resolution Computed Tomography (HRCT) and ventilatory response to exercise in mild to moderate COPD patients.

BACKGROUND AND PURPOSE: In Chronic Obstructive Pulmonary Disease (COPD) patients, the opportunity to carry out a thoracic high-resolution CT (HRCT) scan and to perform an incremental cardiopulmonary exercise test (CPET) increases the possibility to identify the different clinical features of disease. The aim of our study was to evaluate the relationships between HRCT metrics (on emphysema by low attenuation areas-LAA% and airways by wall area-WA%) and CPET variables related to the dynamic response to exercise in terms of elastic balance (Δ rest-to-peak IC/TLC) and ventilation capacity for carbon dioxide output (VE/VCO2slope and VE/VCO2 intercept). METHODS: We prospectively enrolled COPD outpatients from the University Hospital of Parma. Data on anthropometrics characteristics, lung function, HRCT (LAA% and WA%) and CPET (Δ rest-to-peak IC/TLC, VE/VCO2 slope and VE/VCO2 intercept) were recorded. RESULTS: Fifty-one mild to moderate COPD patients (66% males; median age 70 y; mean FEV1 56% of pred.) were enrolled in the study. LAA% demonstrated a significant correlation with Δ rest-to-peak IC/TLC and VE/VCO2slope (r = 0.405, p = 0.005 and r = 0.453, p = 0.001, respectively), while WA% with VE/VCO2slope (r = -0.333, p = 0.020). In multivariate regression models, after adjustment for oxygen uptake (peak VO2) and physical capacity (peak workload), LAA was the only independent predictor of Δ rest-to-peak IC/TLC (ß 0.774, SE 0.334, p = 0.025) and VE/VCO2 slope (ß 0.155, SE 0.053, p = 0.005 and ß 0.305, SE 0.123, p = 0.018, respectively). VE/VCO2 intercept was instead predicted from FEV1 only (ß -0.097, SE 0.042, p = 0.027). CONCLUSION: In mild to moderate COPD patients, emphysema (LAA) and airways metrics (WA) have close relationships with the different characteristics of ventilatory response to exercise. In particular, we were able to show that LAA is an independent predictor of exercise-induced Δ rest-to-peak IC/TLC and VE/VCO2 slope.