High-resolution Computed Tomography Changes Research Articles

Accelerated silicosis in sandblasters: Pathology, mineralogy, and clinical correlates.

With increasing reports of accelerated and acute silicosis, PMF, and autoimmune disease among coal miners and silica-exposed countertop workers, we present previously incompletely-described pulmonary pathology of accelerated silicosis and correlations with mineralogy, radiography, and disease progression in 46 Texas oilfield pipe sandblasters who were biopsied between 1988 and 1995. Worker examinations included pulmonary function tests, chest X-ray (CXR), high-resolution computed tomography (HRCT), and Gallium-67 scans. Quantitative mineralogic analysis of pulmonary parenchymal burden of silica, silicates, and metal particles used scanning electron microscopy with energy dispersive x-ray spectroscopy (SEM EDS). Workers had clinical deterioration after <10 years exposure in dusty workplaces. Althoughinitial CXR was normal in 54%, Gallium-67 scans were positive in 68% of those with normal CXR, indicating pulmonary inflammation. The histology of accelerated silicosis is diffuse interstitial infiltration of macrophages filled with weakly birefringent particles with or without silicotic nodules or alveolar proteinosis. Lung silica concentrations were among the highest in our database, showing a dose-response relationship with CXR, HRCT, and pathologic changes (macrophages, fibrosis, and silicotic nodules). Radiographic scores and diffusing capacity worsened during observation. Silica exposure was intensified, patients presented younger, with shorter exposure, more severe clinical abnormalities, higher lung particle burdens, and more rapid progression in a subset of patients exposed to recycled blasting sand. Accelerated silicosis may present with a normal CXR despite significant histopathology. Multivariable analyses showed silica, and not other particles, is the driver of observed radiologic, physiologic, and histologic outcomes. Eliminating this preventable disease requires higher physician, public health, and societal awareness.

Lung ultrasound and high-resolution computed tomography quantitative variations during nintedanib treatment for systemic sclerosis-associated interstitial lung disease.

Lung ultrasound (LUS) and high-resolution CT (HRCT) are commonly used for the evaluation of interstitial lung disease (ILD). Nintedanib (NIN) is an antifibrotic therapy approved for systemic sclerosis-associated ILD (SSc-ILD). We assessed LUS and quantitative HRCT changes in SSc-ILD patients treated with NIN during a 1 year follow-up, evaluating relationships between imaging variations and functional or quality-of-life outcomes. SSc-ILD patients who started NIN were enrolled and followed for 12 months. Pulmonary function tests and patient-reported outcome measures (PROMs) were assessed half-yearly and quarterly, respectively. LUS was performed quarterly evaluating the presence of B-lines (BL) and pleural line irregularities (PLI). HRCT was repeated after 1 year and quantitatively analysed with CALIPER software. Ten patients (70% female, mean age 62 years) were enrolled. The mean total number of both BL and PLI was constantly decreased during NIN treatment, being significantly reduced after 12 months (from 175.1 [66.7] to 120.8 [70.3] for BL, P = 0.005; and from 50.6 [32.5] to 37.2 [22.4] for PLI, P = 0.05). Male gender, smoking habit and baseline forced vital capacity <70% predicted were associated with worse LUS outcomes. A greater reduction in both BL and PLI was observed in those who improved in PROMs, especially modified Medical Research Council dyspnoea scale (P = 0.016 and P = 0.04, respectively) and Saint George's Respiratory Questionnaire (P = 0.006 and P = 0.026, respectively). No significant changes in the CALIPER percentages of normal parenchyma or ILD elements were observed after 12 months of NIN, thus paralleling the stabilization obtained at pulmonary function tests. We present preliminary results on NIN effects on SSc-ILD as assessed by LUS, a useful method for frequently repeated monitoring, and CALIPER, a valid implementation whenever a HRCT is performed.

Spectrum of high-resolution computed tomography pattern in lungs in patients with connective tissue disorders.

Connective tissue disease associated with interstitial lung disease, or CT-ILD, is a lung condition that affects a large number of patients with a connective tissue disease. Our aim in this study is to correlation between images of high-resolution computed tomography (HRCT) of different connective tissue diseases associated interstitial lung diseases (CTD-ILDs). We shall be aiming to investigate the feasibility of HRCT imaging and thereby avoid lung biopsy in such patients. Rheumatoid arthritis predominantly presented with usual interstitial pneumonia (UIP) (47.8%), followed by nonspecific interstitial pneumonia (NSIP) (30.4%). Mixed connective tissue disorder predominantly presented with NSIP and UIP (42.8%), followed by organizing pneumonia (OP) (14.2%). Systemic lupus erythematosus predominantly presented with UIP (38.8%), followed by NSIP (27.7%). Sjogren's syndrome predominantly presented with lymphocytic interstitial pneumonia (40%), followed by UIP (26.6%). Scleroderma predominantly presented with UIP (45.4%), followed by NSIP (36.4%). Sarcoidosis predominantly presented with UIP (75%), followed by NSIP (25%). Dermatomyositis predominantly presented with NSIP (50%), followed by UIP and OP each (25%). Both clinicians and radiologists should be aware of the expected evolution of HRCT changes in a variety of CT-ILDs.

The outcome of pulmonary function tests and high-resolution computed tomography of chest in post-coronavirus disease 2019-confirmed cases after 3 months of recovery

Background Coronavirus disease (COVID-19) is a recently prevalent infectious disease that is caused by a virus from the coronavirus family and causes acute respiratory syndrome. It is a pandemic catastrophe that has affected more than 60 million people around the world and has caused about 1.5 million deaths, as reported by the WHO. This disease affects the respiratory system and leads to different forms of symptoms and signs. Pneumonia is a common cause for hospitalization, with most patients treated in hospital wards and others requiring ICU. Although the number of complete recoveries from COVID-19 has increased, there is still concern about complications associated with the disease that appear after recovery. The studies that have looked at past types and other forms of coronavirus epidemics, such as SARS have shown that some cases had respiratory complications from the infection after being full recovered, as 36 and 30% of the entire study population had clinical and high-resolution computed tomography (HRCT) changes at 3 and 6 months after recovery, respectively. Mostly, the abnormalities seen in pulmonary function test (PFT) results are sequelae of diffusion capacity defect. In recovered cases of Middle East respiratory syndrome, 36% of patients showed HRCT sequelae at follow-up of 6 weeks, because of fibrosis. Data on COVID-19 indicate that prolonged disease and persistent symptoms show post-PFT affection and follow-up radiographic changes after recovery from COVID-19 as interstitial pulmonary changes and a degree of pulmonary vasculopathy. In recovered cases of COVID-19, capacity of diffusion is the commonest defect in lung function, followed by the restrictive pattern defects on spirometry; both are related to the degree of severity of pneumonic COVID-19. PFTs (involving spirometry as well as diffusion capacity) are considered as routine follow-up examinations for some of the recovered cases, especially severe cases. Rehabilitation programs of the respiratory system are an option strategy that might be considered. This study aims to show changes in pulmonary function and HRCT of chest in post-COVID-19-infected patients to detect long-term effects on the lungs after 3 months as obstructive or restrictive, or both, lung diseases. Patients and methods The study was conducted on 100 confirmed PCR-positive COVID-19 cases that were admitted to Ain Shams University Isolation Hospitals, and the follow-up was performed in the outpatient clinic. PCR samples (Combined nasopharyngeal and oropharyngeal swab) were taken after 3 months from discharge of patients above the age of 18 years who become negative with clinical improvement. PFT [spirometry and diffusion for carbon monoxide (DLCO)] and chest HRCT were done. All patients’ clinical data were recorded, and CT chest imaging data of these patients were correlated with the clinical data. Results A total of 100 patients were included in this study, where males represented 58% and female represented 42%. The mean±SD age of cases in this study was 45.05 ± 11.80 years and ranged from 20 to 79 years. CT chest severity score (SS) of abnormality in COVID-19-infectedd patients based on HRCT chest findings before and after 3 months from treatment showed a highly significant correlation (P=0.000). The results of PFT in the studied group after 3 months of discharge showed restrictive pattern in 14.9%, obstructive pattern in 17.8%, and both obstructive and restrictive patterns in 5.9% of the total number of cases. There was a significant correlation between DLCO abnormality findings and age of studied group (P=0.032), a significant correlation between abnormality findings on PFT and HRCT chest SS after discharge of the studied group (P&lt;0.001). There was a significant correlation between abnormality findings of DLCO and HRCT chest SS after 3 months of the studied group (P=0.000) and before treatment (P=0.001), whereas there was no significant correlation between other findings of PFT and HRCT chest SS after 3 months and before. There was a significant correlation between HRCT chest SS of the studied group and their age after (P=0.003) and before treatment (P=0.000). This cohort study provided the long-term dynamic sequelae and variations of lung function after hospital discharge. Conclusion DLCO-predicted value detected at 3 months is the most important factor associated with severe respiratory COVID-19, which is identified as the cause of impairment of any ordinary basic activity of patients in the stage of postrecovery from COVID-19. The radiological chest findings must be analyzed in conjunction with other functional parameters to provide accurate assessment of the disease. These findings highlight the significance of a comprehensive follow-up after severe and critical COVID-19 infection, with appropriate management of pulmonary consequences. Patients after discharge and on follow-up in outpatient clinics in the post-COVID-19 stage should be strictly followed up with PFTs. Further studies with longer follow-up periods might be needed.

Factors Predictive for Immunomodulatory Therapy Response and Survival in Patients with Hypersensitivity Pneumonitis-Retrospective Cohort Analysis.

The aim of the present retrospective study was to establish predictive factors for treatment success and survival advantage in HP patients. We analyzed the short-term treatment outcome and overall survival in consecutive HP patients treated with prednisone alone or combined with azathioprine. The study group consisted of 93 HP patients, 54 (58%) with fibrotic HP and 39 (42%) with non-fibrotic HP. Mean (± SD) VCmax % pred. and TL,co % pred. before treatment initiation were 81.5 (±20.8)% and 48.3 (±15.7)%, respectively. Mean relative VCmax and TL,co change after 3-6 months of therapy were 9.5 (±18.8)% and 21.4 (±35.2)%, respectively. The short-term treatment outcomes were improvement in 49 (53%) patients, stabilization in 16 (17%) patients, and progression in 28 (30%) patients. Among those with fibrotic HP, improvement was noted in 19 (35%) cases. Significant positive treatment outcome predictors were fever after antigen exposure, lymphocyte count in broncho-alveolar lavage fluid (BALF) exceeding 54%, RV/TLC &gt; 120% pred., and ill-defined centrilobular nodules in high-resolution computed tomography (HRCT). An increased eosinophil count in BALF and fibrosis in HRCT were significant negative treatment outcome predictors. The presence of fibrosis in HRCT remained significant in a multivariate analysis. A positive response to treatment, as well as preserved baseline VCmax (% pred.) and TLC (% pred.), predicted longer survival, while fibrosis in HRCT was related to a worse prognosis. Immunomodulatory treatment may be effective in a significant proportion of patients with HP, including those with fibrotic changes in HRCT. Therefore, future trials are urgently needed to establish the role of immunosuppressive treatment in fibrotic HP.

Changes on chest HRCT in systemic sclerosis-related interstitial lung disease after autologous haematopoietic stem cell transplantation.

To evaluate extent of interstitial lung disease (ILD) and oesophageal involvement using high-resolution computed tomography (HRCT) in early diffuse SSc patients after autologous haematopoietic stem cell transplantation (aHSCT). Overall chest HRCT, lung function and skin score changes were evaluated in 33 consecutive diffuse SSc patients before and after aHSCT during yearly routine follow-up visits between January 2000 and September 2016. Two independent radiologists blindly assessed the ILD extent using semi-quantitative Goh and Wells method, the widest oesophageal diameter (WOD) and the oesophageal volume (OV) on HRCT. Patients were retrospectively classified as radiological responders or non-responders, based on achieved stability or a decrease of 5% or more of HRCT-ILD at 24 months post-aHSCT. Using a linear mixed model, the regressions of the extent of ILD and of ground glass opacities were significant at 12 months (ILD P = 0.001; ground glass opacities P = 0.0001) and at 24 months (ILD P = 0.007; ground glass opacities P = 0.0008) after aHSCT, with 18 patients classified as radiological responders (probability of response 0.78 [95% CI 0.58, 0.90]). Meanwhile the WOD and the OV increased significantly at 12 months (WOD P = 0.03; OV P = 0.34) and at 24 months (WOD P = 0.002; OV P = 0.007). Kaplan-Meier analyses showed a trend towards better 5-year survival rates (100% vs 60%; hazard ratio 0.23 [95% CI 0.03, 1.62], P = 0.11) among radiological responders vs non-responders at 24 month follow-up after aHSCT. Real-world data analysis confirmed significant improvement in extent of HRCT SSc-ILD 24 months after aHSCT, although oesophageal dilatation worsened requiring specific attention.

Lung Function and Symptoms in Post-COVID-19 Patients: A Single-Center Experience.

ObjectiveTo address the lack of information about clinical sequelae of coronavirus disease 2019 (COVID-19).Patients and MethodsPreviously hospitalized COVID-19 patients who were attending the outpatient clinic for post–COVID-19 patients (ASST Ovest Milanese, Magenta, Italy) were included in this retrospective study. They underwent blood draw for complete blood count, C-reactive protein, ferritin, D-dimer, and arterial blood gas analysis and chest high-resolution computed tomography (HRCT) scan. The primary endpoint was the assessment of blood gas exchanges after 3 months. Other endpoints included the assessment of symptoms and chest HRCT scan abnormalities and changes in inflammatory biomarkers after 3 months from hospital admission.ResultsEighty-eight patients (n = 65 men; 73.9%) were included. Admission arterial blood gas analysis showed hypoxia and hypocapnia and an arterial partial pressure of oxygen/fractional inspired oxygen ratio of 271.4 (interquartile range [IQR]: 238-304.7) mm Hg that greatly improved after 3 months (426.19 [IQR: 395.2-461.9] mm Hg, P<.001). Forty percent of patients were still hypocapnic after 3 months. Inflammatory biomarkers dramatically improved after 3 months from hospitalization. Fever, resting dyspnea, and cough were common at hospital admission and improved after 3 months, when dyspnea on exertion and arthralgias arose. On chest HRCT scan, more than half of individuals still presented with interstitial involvement after 3 months. Positive correlations between the interstitial pattern at 3 months and dyspnea on admission were found. C-reactive protein at admission was positively associated with the presence of interstitial involvement at follow-up. The persistence of cough was associated with presence of bronchiectasis and consolidation on follow-up chest HRCT scan.ConclusionWhereas inflammatory biomarker levels normalized after 3 months, signs of lung damage persisted for a longer period. These findings support the need for implementing post–COVID-19 outpatient clinics to closely follow-up COVID-19 patients after hospitalization.

Stratification of long-term outcome in stable idiopathic pulmonary fibrosis by combining longitudinal computed tomography and forced vital capacity.

To test HRCT with either visual or quantitative analysis in both short-term and long-term follow-up of stable IPF against long-term (transplant-free) survival, beyond 2years of disease stability. Fifty-eight IPF patients had FVC measurements and HRCTs at baseline (HRCT0), 10-14months (HRCT1) and 22-26months (HRCT2). Visual scoring, CALIPER quantitative analysis of HRCT measures, and their deltas were evaluated against combined all-cause mortality and lung transplantation by adjusted Cox proportional hazard models at each time interval. At HRCT1, a ≥ 20% relative increase in CALIPER-total lung fibrosis yielded the highest radiological association with outcome (C-statistic 0.62). Moreover, the model combining FVC% drop ≥ 10% and ≥ 20% relative increase of CALIPER-total lung fibrosis improved the stratification of outcome (C-statistic 0.69, high-risk category HR 12.1; landmark analysis at HRCT1 C-statistic 0.66, HR 14.9 and at HRCT2 C-statistic 0.61, HR 21.8). Likewise, at HRCT2, the model combining FVC% decrease trend and ≥ 20% relative increase of CALIPER-pulmonary vessel-related volume (VRS) improved the stratification of outcome (C-statistic 0.65, HR 11.0; landmark analysis at HRCT1 C-statistic 0.62, HR 13.8 and at HRCT2 C-statistic 0.58, HR 12.6). A less robust stratification of outcome distinction was also demonstrated with the categorical visual scoring of disease change. Annual combined CALIPER -FVC changes showed the greatest stratification of long-term outcome in stable IPF patients, beyond 2years. • Longitudinal high-resolution computed tomography (HRCT) data is more helpful than baseline HRCT alone for stratification of long-term outcome in IPF. • HRCT changes by visual or quantitative analysis can be added with benefit to the current spirometric reference standard to improve stratification of long-term outcome in IPF. • HRCT follow-up at 12-14months is more helpful than HRCT follow-up at 23-26months in clinically stable subjects with IPF.

High-Resolution CT Change over Time in Patients with Idiopathic Pulmonary Fibrosis on Antifibrotic Treatment.

Antifibrotic treatment slows down functional decline and disease progression in idiopathic pulmonary fibrosis (IPF). High-resolution computed tomography (HRCT) is useful to diagnose IPF; however, little is known about whether and to what extent HRCT changes reflect functional changes during antifibrotic therapy. The aim of this study was, therefore, to assess HRCT change over time after 1 year of treatment and to evaluate whether these changes correlate with functional decline over the same period of time. Sixty-eight IPF patients on antifibrotic treatment (i.e., pirfenidone or nintedanib) were functionally categorized as stable or progressors based on whether (or not) they had a decline in forced vital capacity (FVC) >5% predicted/year, and their HRCT were scored blindly and independently by two expert thoracic radiologists at treatment initiation (HRCT1) and after 1 year of treatment (HRCT2). Ground glass opacities (Alveolar Score, AS), reticulations (Interstitial Score, IS) and honeycombing (HC) were quantified and correlated with FVC decline between HRCT1 and HRCT2. At treatment initiation, HRCT scores were similar in both stable patients and progressors. After one year of treatment, in the entire population, AS and HC increased significantly, while IS did not. However, when stratified by the rate of functional decline, in stable patients, HC increased significantly while AS and IS did not. On the other hand, among progressors AS and HC increased significantly whereas IS did not. In the entire population, the combined score of fibrosis (IS + HC) correlated significantly with FVC decline. In conclusion, IPF patients on antifibrotic treatment exhibit different patterns of HRCT change over time based on their rate of functional decline. HRCT data should be integrated to lung function data when assessing response to antifibrotic treatment in patients with IPF.

High-resolution computed tomography features of lung disease in perinatally HIV-infected adolescents on combined antiretroviral therapy.

Chronic lung disease is common in perinatally HIV-infected children as they increasingly surviving into adolescence. There are few data on the radiologic spectrum of disease in this population. Contrasted high-resolution computed tomography (HRCT) was performed in ambulatory South African adolescents enrolled in a prospective study of perinatally-infected adolescents aged 9 to 14 years established on combined antiretroviral therapy (cART) and followed for 36 months. Consecutive participants with reduced lung function (defined by a forced expiratory volume in 1 second [FEV1] of <80% normal and/or lung diffusion capacity [DLCO] <80% normal] underwent HRCT. History, clinical, and laboratory data were collected. Two radiologists blinded to clinical data and to each other, reported scans using standardized methodology; a third radiologist resolved discrepancies. Amongst 100 participants undergoing HRCT, median age was 13.8 years (12.8-15.1). The median duration on cART was 8.4 years (IQR = 5.7-9.8). Mosaic attenuation was the most common finding (73%). Of these 71 (91%) demonstrated associated air trapping radiologically consistent with bronchiolitis obliterans. Bronchiectasis occurred in 39% with significant correlation between extent of bronchiectasis and mosaic attenuation (r = 0.57, P < .001). Prior hospitaliszation for childhood pneumonia at any time before enrollment was associated with mosaic attenuation (OR = 3.9, 95%CI, [1.2-12.5]); prior pulmonary tuberculosis (TB) was associated with the combination of mosaic attenuation and bronchiectasis (OR = 4.9, 95%CI, [1.6-15.7]). Most participants (86%) with mosaic attenuation had stage III or IV HIV disease at time of HIV diagnosis (OR = 3.6; [0.9-14.9]). Inter observer agreement between the two readers was good for bronchiectasis (K = 0.71) and moderate for mosaic attenuation (K = 0.51). Despite well-controlled HIV and long duration of cART, HRCT changes were common in perinatally HIV-infected adolescents. There was a high prevalence of small airways disease with and without associated bronchiectasis. These changes were associated with prior pulmonary TB or prior severe pneumonia. Strategies to prevent and treat early life respiratory infection must be strengthened to reduce the burden of chronic lung disease in HIV-infected adolescents.

Longitudinal Changes in Quantitative Interstitial Lung Disease on Computed Tomography after Immunosuppression in the Scleroderma Lung Study II.

The Scleroderma Lung Study II (SLS II) demonstrated significant improvements in pulmonary function and dyspnea at 24 months compared with baseline when patients with symptomatic scleroderma-related interstitial lung disease (SSc-ILD) were treated with either cyclophosphamide for 1 year (followed for another year on placebo) or mycophenolate mofetil for 2 years in a randomized, double-blind clinical trial. Physiologic and clinical outcomes of SLS II have been published previously. The aim of the study was to assess changes from baseline in the extent of SSc-ILD on high-resolution computed tomography (HRCT) measured in the SLS II participants using quantitative image analysis after 2 years and to determine whether these HRCT changes were correlated with the changes in physiologic and clinical measures over the same time interval. Ninety-seven of the 142 randomized subjects (cyclophosphamide group, 47 subjects; mycophenolate mofetil group, 50 subjects) participating in SLS II underwent thoracic volumetric thin-section HRCT at both baseline and 24 months. Quantitative computer-aided diagnosis scores using volumetric HRCT scans were obtained using a previously developed computer-aided system. The scores were quantitative lung fibrosis, quantitative ground glass, quantitative honeycomb, and quantitative interstitial lung disease (QILD), the latter representing the sum of quantitative lung fibrosis, quantitative ground glass, and quantitative honeycomb. These scores were obtained both for the whole lung and for individual lobes. Paired t tests were used for the combined (pooled) cyclophosphamide and mycophenolate mofetil groups to compare 24-month changes from baseline in both the whole lung and the lobe of maximal involvement as determined at baseline (worst lobe). At the end of the 24-month trial, QILD in the whole lung was significantly reduced by a mean of 2.51% in the pooled groups (adjusted 95% confidence interval, -4.00 to -1.03%; P = 0.001). There was no significant difference in the QILD score improvement between the cyclophosphamide (-2.66%) and mycophenolate (-2.38%) groups when assessed separately (P = 0.88). For the pooled group, the 24-month changes in QILD scores in the whole lung correlated significantly with other outcomes, including 24-month changes in forced vital capacity (ρ = -0.37), single-breath diffusing capacity of the lung for carbon monoxide (ρ = -0.22), and breathlessness as measured by the Transition Dyspnea Index (ρ = -0.26). Treatment of SSc-ILD with either cyclophosphamide for 1 year, followed by placebo for a second year, or mycophenolate for 2 years was associated with a significant reduction (improvement) in the extent of HRCT SSc-ILD assessed by computer-aided diagnosis scores, which correlated well with one or more other measures of treatment response. These findings demonstrate that actual changes in lung structure accompany improvements in physiologic and/or symptomatic measures in SSc-ILD.

Chest HRCT findings in patients with primary Sjögren's syndrome.

Pulmonary manifestations (PMs) in primary Sjögren's syndrome (pSS) are among the most frequent extraglandular complications, with reported prevalence varying widely (9-75%), depending on the methods of detection. The aim of this study was to assess the incidence of PMs in pSS and to determine the factors predisposing to the occurrence of this complication. The study group consisted of 68 patients with pSS. Among the patients who were possibly affected by PMs, chest High Resolution Computed Tomography (HRCT) was performed. In the group of all patients afflicted with pSS, 30 people indicated the need to expand medical imaging via chest HRCT scan. (The most frequent reason, in 80%, was persistent, dry cough periodically waking up patients at night). The chest HRCT scan revealed lung tissue changes in the course of 29% of all examined patients (of 68). No correlation was found between the occurrence of HRCT changes and the age of patients (p = 0.8), increased CRP > 5 mg/1 (p = 0.1) or ESR > 20 mm/h (p = 0.9), focus score (p = 0.8), leucopenia (p = 0.5), RF value (p = 0.3), gamma globulin value (p = 0.5), intensity of eye and oral cavity dryness (p = 0.6; 0.3) and smoking cigarettes. Additionally, no correlation was found between more frequent occurrences of antibodies anti-SSA, anti-SSB or anti-Ro52 and HRCT changes (p = 0.3; 0.07; 0.4). Pertaining to the clinical signs, HRCT changes occurred more often only in patients suffering from peripheral arthritis (p < 0.01). PM is a frequent symptom of pSS. A factor predisposing to the development of changes in the respiratory system was not found. Changes in HRCT occur more frequently in patients with peripheral arthritis.

The role of high-resolution computed tomography in the follow-up of diffuse lung disease: Number 2 in the Series "Radiology" Edited by Nicola Sverzellati and Sujal Desai.

High-resolution computed tomography (HRCT) of the lung is a key component of the multidisciplinary approach to diagnosis in diffuse lung disease (DLD). HRCT also plays an important role in the follow-up of patients with established DLD. In this respect, serial HRCT examinations may provide valuable information that cannot be determined from clinical history and other diagnostic tests, such as pulmonary function tests. Important roles of HRCT in this context include assisting in determining prognosis, monitoring for the efficacy of treatment, detecting progression of disease or complications, and evaluating patients with worsening or acute symptoms. Both clinicians and radiologists should be aware of the expected evolution of HRCT changes in a variety of DLDs. The goals of this paper are to discuss: 1) the expected evolution of HRCT findings over time in common DLDs; 2) the role of serial HRCT examinations in formulating an initial diagnosis; and 3) the role of HRCT in the follow-up of patients with known DLD.

COMPLEX CLINICAL AND INSTRUMENTAL EVALUATION OF LUNG INJURY IN PATIENTS WITH RHEUMATOID ARTHRITIS

The damage of the respiratory system is a quite common extra-articular manifestation of rheumatoid arthritis (RA). It is important to note that its clinical symptoms occur in only 20–30% of patients; however, subclinical forms identified by active screening are observed in 70–80% of patients. Objective: to compare the significance of pulmonary complaints, the results of physical examination, and the data of instrumental studies for the detection of lung injury in patients with RA. Subjects and methods. The study enrolled 70 RA patients (63 women and 7 men) aged 24 to 83 years. Only 10% of them had clinically evident lung injury associated with RA. Patients with other pulmonary diseases, such as asthma, chronic obstructive pulmonary disease, etc., were excluded. Physical examination, radiography/fluoroscopy, high-resolution computed tomography (HRCT), single-photon emission computed tomography (SPECT) of the lung, and lung function testing (LFT) with the determination of lung diffusion capacity. Results and discussion. The data of physical examination were nonspecific and unconvincing. Pulmonary complaints (dyspnea, cough, expectoration) were seen in 65% of the patients; an objective assessment revealed changes (vesiculotympanitic resonance, harsh breathing, and pleural friction rub) in 40%. The X-ray films/fluorograms displayed abnormalities (pulmonary fibrosis, focal changes) in only 10% of cases. 92% of the patients had lung HRCT changes including moderate (bronchial obstruction (40%), rheumatoid nodules (10%), ground glass opacities (60%), bronchial thickening (20%), pleural effusion (10%), tree-in-bud opacities (3%)) and severe (pulmonary hypertension (10%), bronchiectasis (10%), emphysema (5%) and lung tissue fibrotic changes as the honeycomb lung (2%)) ones. SPECT showed local hypoperfusion in the mantle and mediastinal parts of the lungs in 80% of cases. LFT analysis demonstrated reduced lung diffusion capacity in 41% of the patients, restrictive disorders in 30%, and bronchial obstruction in 70%. Conclusion. Comparing the clinical and instrumental findings permits one to diagnose subclinical lung injury in patients with RA. Thus, the early detection of pulmonary involvement in RA requires the use of more sensitive methods.

Quantitative Evaluation of High-Resolution CT Findings in Advanced Cystic Fibrosis Patients Based on the Brody Scoring

Background: Progressive destruction of the lungs leads to increased morbidity and mortality rates in patients with CF. In various studies, it has been shown that quantitative evaluation of parenchymal changes in lung high-resolution computed tomography (HRCT) in CF patients measured by the 2006 revised Brody scoring is compatible with the clinical status. CF patients are mostly children who cannot perform complicated pulmonary tests. Unfortunately, screening tests are not performed in many countries, such as Iran, resulting in late diagnosis in older ages, with consequently more diffuse parenchymal involvement and more hospitalization. The quantitative measurement of parenchymal changes in HRCT seems to be useful for early and accurate evaluation of the clinical status. Objectives: The aim of this study was to determine the severity and prevalence of pulmonary changes in late diagnosed CF patients by means of the HRCT Brody scoring system. Patients and Methods: Pulmonary HRCT results of 23 CF patients with the mean age of 13.5 years (5 - 18 years) were scored with the Brody scoring system. The system provided sub-scores for evaluating the presence and severity of five variables in central and peripheral regions of six lung lobes. Results: All studied patients had bronchiectasis and peribronchial wall thickening (PBWT) which were caused by the disease chronicity. However, parenchymal changes in the form of ground glass opacity (GG) and consolidation (CON) were significantly less prevalent, compared to other parameters. The highest score among all lobes was related to bronchiectasis and the lowest to the parenchymal changes (CON, GG). The scoring parameters of bronchiectasis, PBWT, GG, CON, and air trapping showed no significant difference in lobar, central or peripheral involvement, while only mucous plugging was more prominent in the peripheral zones. The contribution of lobar involvement appeared in the following order: right upper lobe (RUL) > left lower lobe (LLL) > right lower lobe (RLL) > left upper lobe (LUL) > Lingula, right middle lobe (RML). Conclusions: It seems that in advanced cases of CF, at older ages and with lack of appropriate medical care, severity, prevalence, and appearance of lung lesions do not follow a definite specific pattern. Therefore, a similar study is suggested in older patients with a larger sample size for comparison of results.

Difficulties in diagnosing severe Pneumocystis jiroveci pneumonia after rituximab therapy for steroid-dependent nephrotic syndrome

Dear Editors, We read with great interest the article by Sato et al., recently published in Pediatric Nephrology, who presented a patient with atypical Pneumocystis jiroveci pneumonia (PCP) with multiple nodular granulomas after rituximab therapy for refractory nephrotic syndrome [1]. We would like to present a case of our patient who, interestingly, revealed a different clinical course compared with that described by Sato and colleagues. An 11-year-old boy with steroid-dependent nephrotic syndrome was on immunosuppression therapy for 9 years. Renal biopsy revealed minimal-change nephrotic syndrome (MCNS). In the course of the disease, he was treated with steroids, cyclophosphamide, levamisole, mycophenolate mofetil, and cyclosporine A (CsA). Because of the high degree of steroid dependency and calcineurin–inhibitor toxicity confirmed on renal biopsy, we decided to start rituximab therapy (RTX). The first course of RTX treatment consisted of two intravenous infusions of 375 mg/m2 given at a weekly interval, with no short- or long-term side effects. Simultaneously, prednisone and CsA at low doses was continued. Six weeks after the first course of RTX, the patient was admitted to our department because of fever 38° C, fatigue even after minimal physical exercise, dyspnea, and tachycardia. Physical examination revealed only stomatitis; laboratory tests showed white blood cell count (WBC) 16.0 g/dl, C-reactive protein (CRP) 10 mg/l, blood urea nitrogen (BUN) and creatinine (Cr) within normal range, depletion of CD19 and CD20 (i.e. <0.01 g/l), and decreased immunoglobulin G (IgG) level. Standard blood and urine cultures were negative, as were blood tests for Chlamydia and Mycoplasma infections as well. Polymerase chain reaction DNA (PCR-DNA) examination excluded cytomegalovirus (CMV) and Epstein Barr virus (EBV) infections. Diagnostic evaluation pointed toward P. jiroveci and consisted of microscopy with staining of an induced sputum specimen, which was negative. Both chest X-ray and high-resolution computed tomography (HRCT) were negative. Although antibiotic therapy with IV azithromycin was started and CsA was tapered, after 7 days, his general condition deteriorated. Because of severe dyspnea, oxygen therapy was initiated, and immunoglobulins were administered. His poor clinical condition, stomatitis, dyspnea, and positive Candida antigen mannan indicated a fungal infection. Caspofungin therapy was started, with no improvement. Due to progressing respiratory failure, the PCP test was repeated (positive microscopy with staining of a subepiglottal smear). Simultaneously, repeated chest HRCT showed massive interstitial changes with crazy-paving and extensive ground-glass patterns. Cotrimoxazole therapy with 120 mg/kg/24 h, i.e. 20 mg/kg/24 h of trimetoprim (TMP) was started [2]. Within a few days of cotrimoxazole introduction, a dramatic improvement in his general status was observed. The therapy was continued for 21 days, followed by a prophylactic dose of TMP: 5.0 mg/kg/day administered orally in equally divided doses twice a day on three consecutive days per week. After 4 weeks of cotrimoxazole therapy, complete resolution of chest HRCT changes was observed. The clinical course of PCP in immunocompromised patients may vary widely: from subtle, almost asymptomatic, as described by Sato and colleagues, to respiratory failure as seen in our patient. Moreover, radiographic findings could be very different: unusual multiple nodular changes in contrast to massive diffuse interstitial pneumonia. Summarizing, we observed gradual deterioration in the general status of our patient, with escalating respiratory failure and no changes in chest HRCT on admission. A fungal infection was recognized, but its treatment did not improve the clinical condition of the patient. We found that negative microscopy with staining of a sputum specimen absolutely does not exclude a PCP infection, and a subepiglottal smear or bronchoscopy with bronchoalveolar lavage should be performed. As did Sato and colleagues, we propose initiating PCP prophylaxis at the beginning of RTX protocol.

A Th17- and Th2-skewed Cytokine Profile in Cystic Fibrosis Lungs Represents a Potential Risk Factor forPseudomonas aeruginosaInfection

Cystic fibrosis (CF) is characterized by progressive pulmonary inflammation that is infection-triggered. Pseudomonas aeruginosa represents a risk factor for deterioration of lung function and reduced life expectancy. To assess T-cell cytokine/chemokine production in clinically stable children with CF and evaluate the association between T-cell subtypes and susceptibility for infection with P. aeruginosa. T-cell cytokine/chemokine profiles were measured in bronchoalveolar lavage fluid (BALF) from children with CF (n = 57; 6.1 ± 5.9 yr) and non-CF control subjects (n = 18; 5.9 ± 4.3 yr). Memory responses to Aspergillus fumigatus and P. aeruginosa were monitored. High-resolution computed tomography-based Helbich score was assessed. In a prospective observational trial the association between BALF cytokine/chemokine profiles and subsequent infection with P. aeruginosa was studied. Th1- (INF-γ), Th2- (IL-5, IL-13), Th17- (IL-17A), and Th17-related cytokines (IL-1β, IL-6) were significantly up-regulated in airways of patients with CF. IL-17A, IL-13, and IL-5 were significantly higher in BALF of symptomatic as compared with clinically asymptomatic patients with CF. IL-17A and IL-5 correlated with the percentage of neutrophils in BALF (r = 0.41, P < 0.05 and r = 0.46, P < 0.05, respectively). Th17- (IL-17A, IL-6, IL-1β, IL-8) and Th2-associated cytokines and chemokines (IL-5, IL-13, TARC/CCL17), but not IFN-γ levels, significantly correlated with high-resolution computed tomography changes (Helbich score; P < 0.05). P. aeruginosa- and A. fumigatus-specific T cells from patients with CF displayed significantly higher IL-5 and IL-17A mRNA expression. IL-17A and TARC/CCL17 were significantly augmented in patients that developed P. aeruginosa infection within 24 months. We propose a role for Th17 and Th2 T cells in chronic inflammation in lungs of patients with CF. High concentrations of these cytokines/chemokines in CF airways precede infection with P. aeruginosa.

Pulmonary infections caused by non-tuberculous mycobacteria−single centre experience

Introduction. Non-tuberculosis mycobacteria are environmental organisms found in soil and water worldwide, and an infection caused by non-tuberculosis mycobacteria is less frequently found than the one associated with Mycobacterium tuberculosis. This study was designed to evaluate data relating to non-tuberculosis mycobacteria in patients with clinical importance. Material and Methods. Of 12 patients (pts) admitted to the Department of Pulmonology, Clinical Centre of Serbia in Belgrade during 2010- 2011, seven (58.33%) were men and five (41.67%) were women. Bacteriological and radiographic findings, co?morbidity, treatment management and outcome were evaluated from medical records. Results. Using GenoType? Mycobacterium CM/AS (Hain Lifescience) assays for identification of isolated cultures of NTM) M.xenopi was found in six (50%) pts, M.avium complex in two (16.67%) pts, M.kansasii and M.xenopi in one (8.33%), M. gordone, M.abscessus and M.peregrinum in one (8.33%) patient each. Cavitary lesions were most frequently determined on high resolution computed tomography in five (41.67%) pts, followed with consolidation in two (16.67%) pts, cavitation with fibronodular lesions and bronchiectasis in one (8.33%) patient each. Comorbidities were noticed in nine (75%) pts, with chronic obstructive pulmonary diseases most frequently found in six (50%) pts. According to American Thoracic Society definition and criteria, treatment was administered in nine (75%) pts. Conclusion. In order to find the right treatment, it is important to identify non-tuberculosis mycobacteria lung infection by culture methods, at least two positive, accompanied with high resolution computed tomography changes.

CT findings related to exposure to polyvinyl chloride

Although some adverse health effects of exposure to polyvinyl chloride (PVC) are well known, there is limited evidence of its effects on the respiratory system. To assess the pulmonary effects of exposure to PVC with high-resolution computed tomography (HRCT). Workers and administrative staff of two PVC production plants completed questionnaires and went through pulmonary function testing and HRCT. Analysis of PVC dust in the work environment was performed by the Directorate of Occupational Health and Safety. In total, 104 PVC-exposed workers and 43 administrative controls participated. HRCT revealed pleural and/or parenchymal changes in 55% of the exposed subjects. Pleural thickening was detected in 14 subjects, 13 of whom were in the exposed group (P < 0.05). Isolated pleural thickening without parenchymal involvement was present in seven workers, who were all in the exposed group (P < 0.05). Pleural thickening was frequently bilateral and localized to the parietal and visceral pleura. Round opacities, heterogeneous attenuation and ground-glass opacities were only detected in the exposed group (P < 0.05). Exposure to dust increased the risk of findings on HRCT (odds ratio (OR) 4.2, P < 0.05). There were no correlations between pulmonary function tests or respiratory symptoms and HRCT findings. HRCT changes were more common in subjects with forced mid-expiratory flow (FEF(25-75)) < 50% (P < 0.001). This study found that exposure to PVC dust, at levels below the legal limit for respirable particulate matter, was associated with parenchymal changes and pleural thickening on HRCT.

Follow-up in pulmonary sarcoidosis: comparison between HRCT and pulmonary function tests

The authors assessed the clinical usefulness of high-resolution computed tomography (HRCT) for monitoring sarcoidosis by comparing changes on HRCT with those on pulmonary function test (PFT) results over time. The baseline and follow-up (after 13 months, range 15-63 months) HRCT scans of 14 consecutive patients with sarcoidosis were reviewed by a single observer. Each follow-up HRCT examination was assessed as stable, improved (when the extent of HRCT findings was reduced compared with baseline) and worsened (when the extent of HRCT findings was increased and/or when HRCT pattern had become fibrotic compared with baseline). Any increase or decrease in forced vital capacity (FVC)≥10% from baseline was considered significant. Changes on HRCT were then compared with those on FVC. During a median follow-up of 33 (range 15-63) months, HRCT findings worsened in 8/14 (58%) cases, improved in 3/14 (21%) and remained stable in 3/14 (21%). Agreement between changes on HRCT and FVC was moderate (κ=0.49). In 9/14 (64%) cases, HRCT changes were in line with those on FVC. In 4/5 discordant cases, the worsened HRCT findings were not mirrored by FVC changes. Despite the small size of our study population, our results suggest that HRCT may provide clinicians with additional information about the evolution of sarcoidosis.