High-resolution Computed Tomography Patterns Research Articles

Standard national high-resolution computed tomography (HRCT) Protocol: A Recommendation by The Royal College of Radiologists of Thailand (RCRT) and Thoracic Society of Thailand Under Royal Patronage (T.S.T.)

Diffuse interstitial lung diseases (ILDs) include more than hundreds of diseases which have different causes or underlying, target groups, signs and symptoms, clinical courses, radiographic appearances, treatments, and prognosis. Among them, idiopathic pulmonary fibrosis (IPF) is the most fatal, with prognosis worse than many cancers. After decades of no specific treatment, new medications that may help slow the progression of the fibrosis have been introduced and approved in some countries. Similar to corticosteroid, anti-inflammatory and immunosuppressive drugs which are used to treat some ILDs; these antifibrotic medications could cause certain side effects. In contrast, the cost of treatment is much higher. To monitor ILDs in terms of incidence, demographic and geographic distributions, and life expectancy; T.S.T. is developing a national ILD database. To ensure that this data base will provide the most accurate information, diagnosis should be as much precise as possible. However, the diagnoses of most ILDs are multidisciplinary. With the facts that surgical lung biopsies are available in patients fewer than 20% in most countries1, HRCT plays important role in showing disease characters and extension. Certain HRCT patterns are accepted to replace surgical lung biopsies (SLB) in some diseases. Unfortunately typical diagnostic HRCT patterns to replace SLB are not possible in all cases; for example, only about half of usual interstitial pneumonia2. Initially, diagnosis could not be made in some cases whose HRCT patterns are not specific and other clinical information is not sufficient. Longitudinal study by following up HRCTs and adding subsequently exhibited clinical data, or even surgical lung biopsy, could eventually establish the diagnosis. These patients need a system that provide regular clinical and HRCT follow up, also the multidisciplinary team to evaluate those newly acquired clinical and radiographic information . As an important role in managing patients with ILDs, standard HRCT is required to ensure that the initial examination will provide sufficient radiographic information, both the initial and follow-up examinations could be compared, the interpretation of all examinations is reproducible, and it could be performed in most institutes. To develop national standard HRCT protocol; current situation of interstitial lung diseases in Thailand,the purpose to develop the protocol, and a probable draft of the standard protocol (made by the committee from RCRT) were presented to a panel consisted of thoracic radiologist experts from all parts of Thailand in a meeting held on 11 January 2019 by Foundation of Orphan and Rare Lung Disease (FORD) and Imaging Academic Outreach Center (iAOC). Knowledge sharing, benefits and disadvantages of the drafted protocol were discussed. Adjustment was done based on feasibility, coverage of all lung diseases, diagnostic accuracy, and radiation safety. The panel provided a standard protocol describing scan coverage, technique, collimation, rotation time, pitch, radiation dose, and reconstruction images. The standard protocol recommends a mandatory acquisition for the first HRCT and optional or additional ones for the follow-up or particular cases.

Standard national high-resolution computed tomography (HRCT) Protocol

Diffuse interstitial lung diseases (ILDs) include more than hundreds of diseases which have different causes or underlying, target groups, signs and symptoms, clinical courses, radiographic appearances, treatments, and prognosis. Among them, idiopathic pulmonary fibrosis (IPF) is the most fatal, with prognosis worse than many cancers. After decades of no specific treatment, new medications that may help slow the progression of the fibrosis have been introduced and approved in some countries. Similar to corticosteroid, anti-inflammatory and immunosuppressive drugs which are used to treat some ILDs; these antifibrotic medications could cause certain side effects. In contrast, the cost of treatment is much higher.
 To monitor ILDs in terms of incidence, demographic and geographic distributions, and life expectancy; T.S.T. is developing a national ILD database. To ensure that this data base will provide the most accurate information, diagnosis should be as much precise as possible.
 However, the diagnoses of most ILDs are multidisciplinary. With the facts that surgical lung biopsies are available in patients fewer than 20% in most countries1, HRCT plays important role in showing disease characters and extension. Certain HRCT patterns are accepted to replace surgical lung biopsies (SLB) in some diseases.
 Unfortunately typical diagnostic HRCT patterns to replace SLB are not possible in all cases; for example, only about half of usual interstitial pneumonia2. Initially, diagnosis could not be made in some cases whose HRCT patterns are not specific and other clinical information is not sufficient. Longitudinal study by following up HRCTs and adding subsequently exhibited clinical data, or even surgical lung biopsy, could eventually establish the diagnosis. These patients need a system that provide regular clinical and HRCT follow up, also the multidisciplinary team to evaluate those newly acquired clinical and radiographic information .
 As an important role in managing patients with ILDs, standard HRCT is required to ensure that the initial examination will provide sufficient radiographic information, both the initial and follow-up examinations could be compared, the interpretation of all examinations is reproducible, and it could be performed in most institutes.
 To develop national standard HRCT protocol; current situation of interstitial lung diseases in Thailand,the purpose to develop the protocol, and a probable draft of the standard protocol (made by the committee from RCRT) were presented to a panel consisted of thoracic radiologist experts from all parts of Thailand in a meeting held on 11 January 2019 by Foundation of Orphan and Rare Lung Disease (FORD) and Imaging Academic Outreach Center (iAOC). Knowledge sharing, benefits and disadvantages of the drafted protocol were discussed. Adjustment was done based on feasibility, coverage of all lung diseases, diagnostic accuracy, and radiation safety.
 The panel provided a standard protocol describing scan coverage, technique, collimation, rotation time, pitch, radiation dose, and reconstruction images. The standard protocol recommends a mandatory acquisition for the first HRCT and optional or additional ones for the follow-up or particular cases.

Role of telomerase expression in interstitial lung diseases

BackgroundTelomeres are hexameric nucleotide sequences. The biological role of telomeres is to prevent shortening of DNA to preserve integrity of the genome. Length of telomeres is determined by age, sex, and environmental exposures. Telomeres are vulnerable to injury by oxidative stress. Telomere length is sustained by telomerase, a ribonucleoprotein telomerase reverse transcriptase (TERT). Telomerase may help cell growth and secure against cell death. ‘Telomeropathy’ is associated with genetic mutations. The most common phenotype related to telomerase mutation is pulmonary fibrosis.ObjectiveTo investigate the associations of both TERT and telomerase RNA component C with disease progression in patients with interstitial lung diseases (ILDs), which include idiopathic pulmonary fibrosis (IPF), and to compare results between patients with ILD and control.Patients and methodsA total of 46 patients with different types of ILDs were enrolled as well as 15 healthy persons as control. Whole blood sample was obtained from both patients and healthy control for detection of expression of telomerase gene by quantitative real-time PCR.ResultsThere was a significant negative correlation between telomerase reverse transcriptase (h-TERT) and partial pressure of oxygen (r=−23, P=0.03). Both h-TERT and telomerase reverse transcriptaseRNA component (h-TERC) were relatively more expressed in patients with IPF with pulmonary hypertension, whereas there was a significant elevation of h-TERT relative expression in patients with IPF with honeycombing high-resolution computed tomography pattern in comparison with those with reticulonodular pattern, with median of 0.85 versus 0.29, respectively.ConclusionHypoxia may affect DNA damage in the telomere region. Expression of telomerase may take part in pulmonary fibrosis. Exposure to hypoxia or growth factors can stimulate the expression of telomerase on cells of vascular smooth muscle.

Clinicoradiological Features of Pulmonary Tuberculosis with Interstitial Pneumonia.

Objective Although rare, pulmonary tuberculosis occasionally develops in patients with interstitial pneumonia (IP). In this study, we aimed to evaluate the clinicoradiological features of pulmonary tuberculosis associated with IP. Methods In this retrospective, observational, single-center study, the medical charts, high-resolution computed tomography (HRCT) findings, and bacteriological test results of patients with IP who also tested positive for Mycobacterium tuberculosis were reviewed. Patients The study included 20 patients with IP out of 329 who tested positive for M. tuberculosis in sputum or bronchoalveolar lavage fluid cultures at Toranomon Hospital between January 2006 and December 2017. Results The HRCT patterns were usual interstitial pneumonia (UIP) in 11 patients and non-UIP in 9 patients. Consolidations (80%) were the most frequent HRCT findings, followed by cavities (60%) and nodules (45%), which are generally characteristic of pulmonary tuberculosis. Consolidations often developed in relation to fibrotic or emphysematous lesions. Tuberculosis lesions could not be identified in one patient. All patients were treated with anti-tuberculosis drugs according to WHO guidelines, and 13 patients achieved a WHO category of “Treatment success.” No patient died of tuberculosis, and the median survival time for the 20 patients was 1,196 days. Conclusion Although the HRCT findings for pulmonary tuberculosis associated with IP are atypical, appropriate tuberculosis treatments can lead to favorable outcomes.

Plasma surfactant protein-D as a potential biomarker in idiopathic pulmonary fibrosis

ObjectivesIdiopathic pulmonary fibrosis (IPF) is a disease of an increasing burden. Its diagnosis is based on definite high-resolution computed tomography pattern and is associated with the histopathological and/or radiological pattern of usual interstitial pneumonia with exclusion of other causes of interstitial pneumonia. The surfactant protein-D (SP-D) level in the serum is measured in several lung diseases, including IPF.Aim of studyThe aim of the current study is to assess the serum level of SP-D as a potential biomarker to distinguish between IPF and other idiopathic interstitial pneumonia patients.Patients and methodsThis study was conducted in the Chest Department, Kasr Al Ainy Hospitals, Cairo University. The study population included 20 healthy controls, 20 IPF patients, and 18 other idiopathic interstitial pneumonia patients. All were subjected to full history taking, clinical examination, high-resolution computed tomography chest, spirometry, arterial blood gases, blood samples for measuring SP-D by enzyme-linked immunosorbent assay.ResultsThere was no statistical significance between the serum level of SP-D in IPF and non-IPF patients, however, there was a significant increase in the serum level of SP-D in IPF patients diagnosed at a late stage compared with those diagnosed at an early stage and those on anti-fibrotic therapy. Also, there was a statistical significance between the degree of clubbing and gastroesophageal reflux disease and the serum level of SP-D with a P value of 0.005 and 0.029, respectively. Serum SP-D level had a negative correlation with more severe form of the disease regarding the duration of illness, forced vital capacity percent, and it had a significant negative correlation with oxygen saturation and 6 min walk distance with a P value of 0.023 and 0.005, respectively.ConclusionThe level of serum SP-D level in IPF patients correlate well with the severity of the disease and could be a possible marker to use for the follow up of patients on anti-fibrotic drugs.

Analysis of systemic lupus erythematosus-related interstitial pneumonia: a retrospective multicentre study

Thoracic diseases in patients with systemic lupus erythematosus (SLE), especially interstitial pneumonia (SLE-IP), are rare and have been poorly studied. The aims of this multicentre study were to evaluate SLE-IP and elucidate its clinical characteristics and prognosis. Fifty-five patients with SLE-IP who had attended the respiratory departments of participating hospitals were retrospectively evaluated in this multicentre study. Clinical information, high-resolution computed tomography (HRCT), and surgical lung biopsy/autopsy specimens were analysed by respiratory physicians, pulmonary radiologists, and pulmonary pathologists. IP patterns on HRCT and lung specimens were classified based on the international classification statement/guideline for idiopathic interstitial pneumonias. The most frequent form of SLE-IP at diagnosis was chronic IP (63.6%), followed by subacute (20.0%), and acute IP (12.7%). Radiologically, the most common HRCT pattern was “Unclassifiable” (54%). Histologically, “Unclassifiable” was the most frequently found (41.7%) among 12 patients with histologically proven IP. Interestingly, accompanying airway diseases were present in nine of these patients (75%). In multivariate analysis, current smoking (hazard ratio [HR] 6.105, p = 0.027), thrombocytopenia (HR 7.676, p = 0.010), anti-double-strand DNA titre (HR 0.956, p = 0.027), and nonspecific interstitial pneumonia (NSIP) + organizing pneumonia (OP) pattern on HRCT (vs. NSIP, HR 0.089, p = 0.023) were significant prognostic factors. In conclusion, chronic IP was the most frequent form of IP in patients with SLE-IP, and “Unclassifiable” was the commonest pattern radiologically and histologically.

Lung HRCT pattern classification for cystic fibrosis using convolutional neural network

Cystic fibrosis (CF) is one of the most prevalent autosomal recessive disorders among whites. It mostly affects lungs which causes infection and inflammation leading to 90% of deaths among CF patients. Due to wide variability in its clinical presentation and organ involvement, studying responses to therapy and evaluation of pulmonary changes over time is crucial in progress prevention of CF. Serial high-resolution computed tomography (HRCT) scans significantly facilitate the assessment of the pulmonary abnormalities evolution in CF patients. Recently, artificial intelligence is being employed for analyzing thoracic CT scans acquired from CF patients. In this paper, we propose a convolutional neural network (CNN) approach for classifying CF lung patterns in HRCT images. The proposed network consists of two convolutional layers with 3 × 3 kernels and max-pooling in each layer followed by two dense layers of 1024 and 10 neurons, respectively. The softmax layer prepares a probabilistic distribution of predicted output among classes. This layer has three outputs, equivalent to the classes corresponding to normal (healthy), bronchiectasis, and inflammation. To train and evaluate the network, we built up a patch-based dataset extracted from more than 1100 lung HRCT slices which were acquired from 45 CF patients. A comparative evaluation proved the effectiveness of the proposed CNN with respect to its close counterparts. The classification accuracy, mean sensitivity, and specificity of 93.64%, 93.47%, and 96.61% were achieved which demonstrated the potential of CNNs in analyzing lung CF patterns and following up the lungs’ status. In addition, the visual features extracted by our proposed method might be helpful for automatic measurement and eventually scoring the severity of CF patterns in lung HRCT images.

Lung Diseases in Inflammatory Myopathies.

Lung involvement is the leading cause of mortality in inflammatory myopathy. A careful assessment of clinical and serologic manifestations especially myositis-associated autoantibodies allows precise classification of the different phenotypes of inflammatory myopathy and stratification of the risk of lung involvement. About three out of four patients with inflammatory myopathy develop interstitial lung disease (ILD), which represents the main cause of morbidity and mortality. In patients with a confirmed diagnosis of inflammatory myopathy, the approach to the diagnosis of ILD includes assessment of clinical and functional severity, evaluation of the high-resolution computed tomography pattern of disease, which often suggests nonspecific interstitial pneumonia or organizing pneumonia. Bronchoalveolar lavage to rule out infection is often performed; however, video-assisted thoracoscopic lung biopsy is now generally discouraged, unless malignancy is suspected. The so-called antisynthetase syndrome characterized by the combination of mechanics' hands, Raynaud' phenomenon, myositis often mild or absent, and presence of one of the anti-tRNA synthetase antibodies is associated with a 70% risk of ILD, especially in subjects with antibodies other than anti-Jo1 antibodies (i.e., anti-PL7 or -PL12 antibodies). Treatment depends on both severity and progression of ILD, often including a combination of corticosteroids and immunosuppressive therapy. Rituximab-based regimen has showed promising results in retrospective studies for the management of refractory or rapidly progressive forms of ILD. Clinical trials are ongoing to evaluate the actual efficacy of this strategy on mortality related to lung disease. Secondary pulmonary complications of inflammatory myopathy include opportunistic infections, aspiration pneumonia, pneumomediastinum, ventilatory failure due to diaphragmatic muscular weakness, drug-induced pneumonitis, and rarely pulmonary hypertension.

Prognostic factors of interstitial lung disease progression at sequential HRCT in anti-synthetase syndrome.

Interstitial lung disease (ILD) is a common extra-muscular manifestation of anti-synthetase syndrome (ASS) and the main cause of morbidity and mortality in patients with ASS. Data on prognostic factors in these patients are lacking. A total of 69 patients with ILD and positivity for at least one of the following autoantibodies were included: anti-Jo-1, anti-PL7, anti-PL12, and anti-EJ. Relevant clinical characteristics were registered. According to the changes in the extent of abnormalities at the follow-up on high-resolution computed tomography (HRCT), three groups were defined: the regression, stability, and deterioration groups. Univariate analysis was performed to evaluate possible prognostic factors and multivariate analysis by logistic regression was then applied to determine the independent prognostic factors in ASS-ILD. The cohort comprised 69 patients positive for anti-synthetase antibodies, i.e., 30 for anti-Jo-1, 16 for anti-EJ, 13 for anti-PL7, and 10 for anti-PL12. The mean length of follow-up was 15months. Sex, age at diagnosis, fever at presentation, and counts of CD3+CD4+ cells were significantly different among the three groups. According to the multivariate analysis, fever at presentation, lower counts of CD3+CD4+ cells, and a pattern of usual interstitial pneumonia were the three independent risk factors for poor outcomes of ASS-ILD. At the onset of ASS, some clinical features and HRCT pattern of ILD may suggest an unfavorable outcome of lung involvement on HRCT, even with routine therapy. These factors may contribute to the high long-term mortality of ASS. • Evaluation of lung involvement on HRCT is important in the follow-up of patients with interstitial lung disease related to anti-synthetase syndrome (ASS-ILD). • The interstitial lung disease related to ASS responds to the treatment variably. • Some clinical and imaging characteristics are associated with poor prognosis in patients with ASS-ILD, including fever at diagnosis, a lower serum CD3 + /CD4 + level, and a UIP pattern.

Radiological patterns of pulmonary involvement may predict treatment response in rheumatoid arthritis: A retrospective study.

There have been no reports on the relationship between lung radiological patterns and rheumatoid arthritis (RA) disease activity or RA treatment response in patients with RA-associated lung disease (RA-LD). Patients with RA-LD who underwent treatment for RA from April 2005 to March 2015 were retrospectively evaluated. RA-LD patients were divided into three groups based on high-resolution computed tomography (HRCT) patterns [usual interstitial pneumonia (UIP), nonspecific interstitial pneumonia (NSIP), and bronchiolitis]. The disease activity score of 28 joints-erythrocyte sedimentation rate (DAS28-ESR) and the response of RA to treatment, as measured by the European League Against Rheumatism (EULAR) response criteria, were investigated. A total of 77 patients (21 with UIP, 23 with NSIP, and 33 with bronchiolitis) were enrolled. Median scores (interquartile range) on the DAS28-ESR at baseline were 5.27 (4.76-5.74), 5.48 (4.24-6.34), and 5.04 (3.90-5.66) for UIP, NSIP, and bronchiolitis, respectively; there were no statistical differences between the three groups (p = 0.412). One year after baseline, 19 (90%), 14 (61%), and 19 (58%) of patients in the UIP, NSIP, and bronchiolitis groups, respectively, were considered good or moderate responders, as evaluated using the EULAR response criteria; there was a significant difference between these three groups (p = 0.014). Multiple logistic regression analysis revealed that the UIP pattern was significantly associated with good or moderate response to RA treatment 1 year after baseline (p = 0.012). These results suggest that NSIP and bronchiolitis HRCT patterns may be risk factors for resistance to RA therapy.

Clinical characteristics and outcome in patients with antisynthetase syndrome associated interstitial lung disease: a retrospective cohort study

ABSTRACTBackground and objective: To describe the clinical characteristics including the bronchoalveolar lavage fluid (BALF) characteristics of patients with antisynthetase syndrome (AS) associated interstitial lung disease (ILD) in a tertiary ILD outpatient clinic, their medical therapy and outcome.Methods: Retrospective cohort study of patients with AS-ILD. All available data of clinical characteristics, pulmonary function tests, laboratory parameters, BALF analysis, histology, high-resolution computed tomography (HRCT) and treatment were collected from the patient files.Results and conclusions: Twelve patients with AS-ILD were identified. Mean age at diagnosis was 55 years (range 45–69), 67% were female. Mean follow-up time was 7 years. The anti-aminoacyl tRNA-synthetase antibodies presented were anti-Jo1 (n = 6), anti-PL7 (n = 3), anti-PL12 (n = 2) and anti-EJ (n = 1). HRCT patterns were mainly non-specific interstitial pneumonia (75%). Four patients had BALF-eosinophilia (two of four anti-Jo1 patients) and two anti-PL12 positive patients had BALF-neutrophilia. Two AS-ILD patients improved on rituximab (RTX) as induction treatment and three out of four patients were stabilised on RTX as maintenance treatment. Two patient obtained remission by cyclophosphamide. Four patients were stabilised on azathioprine alone or in combination with oral corticosteroids.Our cohort of AS-ILD patients showed clinical characteristics in accordance with previous reports at baseline and was comparable to other cohorts. Most patients can be stabilised with immunosuppressive treatment.

MOLECULAR DIAGNOSIS OF USUAL INTERSTITIAL PNEUMONIA (UIP) FROM TRANSBRONCHIAL BIOPSY IS ACCURATE IN SUBJECTS WITHOUT DEFINITE OR PROBABLE UIP ON CT

SESSION TITLE: Diagnosis and Treatment of Idiopathic Pulmonary Fibrosis SESSION TYPE: Original Investigations PRESENTED ON: 10/08/2018 07:30 am - 08:30 am PURPOSE: Under the diagnostic criteria for idiopathic pulmonary fibrosis (IPF) recently proposed by the Fleischner Society, histologic confirmation of UIP by tissue biopsy is necessary for a confident diagnosis of IPF if high-resolution computed tomography (HRCT) does not show either definite or probable usual interstitial pneumonia (UIP), in the clinical context of an idiopathic interstitial pneumonia. If histopathology is not available or not definitive, a working IPF diagnosis may be appropriate. The Envisia Genomic Classifier (Envisia) detects UIP at the molecular level (‘molecular UIP’) in transbronchial biopsy samples, using a locked machine learning algorithm applied to the expression of 190 genes. In a prospective, multi-center validation study of 49 subjects undergoing clinical evaluation for new-onset interstitial lung disease (BRonchial sAmple collection for a noVel gEnomic test, BRAVE), Envisia shows 88% specificity and 70% sensitivity for histopathology-proven UIP. We report Envisia performance in validation cohort subjects who had HRCT patterns other than definite or probable UIP, determined by local radiology diagnoses and by central radiology review. METHODS: HRCT scans and diagnoses were obtained from BRAVE sites. Available scans were reviewed by an expert thoracic radiologist and diagnosed as definite UIP, probable UIP, possible UIP, non-UIP or ‘other’. For categorical comparison (Cohen’s kappa), specific non-UIP and ‘other’ diagnoses were defined as ‘inconsistent with UIP’. RESULTS: 46 of 49 validation subjects had available HRCT scans. Diagnostic agreement between local and central radiology was low (kappa= 0.28), but improved when confident UIP (definite or probable UIP) was compared to those with either possible UIP or a pattern inconsistent with UIP (kappa =0.49). We excluded 4 subjects with definite or probable UIP patterns by both local and central radiology, as these subjects would be considered already to have a confident diagnosis. Among 42 subjects without definite or probable UIP on HRCT (40% UIP prevalence by histopathology), Envisia showed specificity of 88% [CI:69%-97%], sensitivity of 76% [CI:50%-93%], positive predictive value of 81% [54%-96%] and negative predictive value of 85% [CI:65%-96%]. CONCLUSIONS: In a retrospective analysis of subjects with HRCT patterns other than definite or probable UIP, Envisia molecular UIP had >80% predictive value for histologically-proven UIP. CLINICAL IMPLICATIONS: Molecular UIP results may be useful in the multidisciplinary evaluation of subjects without high-confidence HRCT patterns, who are being considered for surgical biopsy. In the appropriate clinical context, the high predictive value of molecular UIP may support confident IPF diagnosis without surgery. 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Diagnostic Yield of Computed Tomography-Guided Transthoracic Lung Biopsy in Diffuse Lung Diseases

Background: Accurate diagnosis is essential for successful management of diffuse lung disease (DLD). Histopathology may sometimes be necessary. Surgical lung biopsy, the gold standard, carries a risk of morbidity and mortality. Computed tomography (CT) guided transthoracic lung biopsy (CT-TLB) is a minimally invasive method for obtaining lung tissue. However, its diagnostic yield is unknown in DLD. Objective: To assess the diagnostic yield of CT-TLB in DLD according to the predominant high-resolution CT (HRCT) patterns. Methods: Between January 2009 and December 2016, we enrolled all consecutive adult patients with suspicion of DLD who underwent CT-guided transthoracic lung biopsy during the diagnostic work-up. All biopsies were performed by a senior interventional radiologist using CT fluoroscopy. Results: The study included 169 patients (50.3% men) with a mean (±SD) age of 58.3 ± 14 years. Consolidation was the predominant HRCT pattern. A definitive or probable diagnosis was made in 66.3%. The most frequent diagnosis was organizing pneumonia (36.2%). Diagnostic yield was higher when the predominant HRCT pattern was consolidation or nodular. The most common complication was pneumothorax (17.8%); other complications included mild hemoptysis (7.7%), hemothorax (1.2%), and death (0.59%). No acute exacerbation of the underlying condition was observed. Conclusions: CT-TLB proved to be accurate and safe for the diagnosis of DLD. The overall diagnostic yield of the procedure was 66.3%. Given its low complication rates, CT-TLB can be an option in patients whose respiratory function is seriously impaired and in those with substantial comorbidities, where more invasive procedures cannot be performed for reasons of safety.

Serum concentration of surfactant protein D in patients with systemic sclerosis: The potential marker of the interstitial lung disease severity.

Pulmonary involvement is a severe manifestation of systemic sclerosis (SSc). The study was designed to determine the serum level of surfactant protein D (SP-D) in patients with SSc in relation to clinical and laboratory parameters as well as to analyze dynamics of changes of these indices within one year of observation. SP-D was assayed in 41 patients with SSc and 15 healthy controls. Additionally, pulmonary function tests, chest high-resolution computed tomography (HRCT), and inflammatory markers were assessed. All tests were performed twice: at entry and repeated after one year of observation. The serum level of SP-D was significantly higher in patients with SSc than in healthy controls. Serum concentration of SP-D was significantly higher in patients with systemic sclerosis-related interstitial lung disease (SSc-ILD) than in those without SSc-ILD. SP-D was found to correlate with lung involvement evaluated with the Medsger score (diffusing capacity of the lung for carbon monoxide (DLCO), forced vital capacity, radiological changes, and estimated pressure in the pulmonary artery in echocardiography). SP-D correlated with the honeycombing and/or reticular pattern in HRCT and ground glass opacification pattern. Serum concentration of SP-D was elevated in patients with a decreased DLCO. Furthermore, SP-D was higher in patients with diffuse cutaneous type (dcSSc) of the disease than in those with SSc limited type (lcSSc). Because of the small size of the group, it was not possible to perform a statistical analysis for patients who had different results in HRCT, VC, and Medsger score between the first and the second evaluation. SP-D seems to be an index for assessing lung involvement. It reflects the state of pulmonary fibrosis but not the dynamics of the pulmonary fibrosis progression. Further studies are needed to evaluate clinical application of the index, and currently, there is no evidence for the recommendation of the application of SP-D in routine evaluation of patients with SSc.

Cryobiopsies are diagnostic in Pleuroparenchymal and Airway-centered Fibroelastosis

BackgroundIdiopathic pulmonary fibroelastosis (iPPFE) is a rare lung lesion characterized by pleural and subpleural parenchymal thickening due to accumulation of fibroelastotic tissue. Only recently, a few cases with a peribronchiolar distribution of fibroelastotic tissue have been reported. These lesions are more prominent in the upper lobes. Even though high resolution computed tomography (HRCT) scan features are considered characteristic, a histological confirmation is suggested, mainly when the clinical setting is not clearly defined. However, due to non-negligible complications, a surgical lung biopsy is not often recommended. The prognosis is usually poor and currently, the only effective treatment is lung transplantation.MethodPatients with a multidisciplinary diagnosis of iPPFE or airway-centered fibroelastosis (airway-centered FE), with histological confirmation by transbronchial cryobiopsy, were identified from an ongoing interstitial lung disease registry. Data on patient demographics, HRCT patterns, size and number of biopsies, histology patterns and complications were registered.ResultsSeven patients were diagnosed with iPPFE and one patient was diagnosed with airway-centered FE. Pneumothorax was documented in three cases, but none of them required a chest tube. No other complications during or after the procedure were observed.ConclusionThis study suggests that using cryobiopsies in the diagnostics of PPFE and airway-centered FE is safe and effective.

\u201cVelcro-type\u201d crackles predict specific radiologic features of fibrotic interstitial lung disease

Background“Velcro-type” crackles on chest auscultation are considered a typical acoustic finding of Fibrotic Interstitial Lung Disease (FILD), however whether they may have a role in the early detection of these disorders has been unknown. This study investigated how “Velcro-type” crackles correlate with the presence of distinct patterns of FILD and individual radiologic features of pulmonary fibrosis on High Resolution Computed Tomography (HRCT).MethodsLung sounds were digitally recorded from subjects immediately prior to undergoing clinically indicated chest HRCT. Audio files were independently assessed by two chest physicians and both full volume and single HRCT sections corresponding to the recording sites were extracted. The relationships between audible “Velcro-type” crackles and radiologic HRCT patterns and individual features of pulmonary fibrosis were investigated using multivariate regression models.Results148 subjects were enrolled: bilateral “Velcro-type” crackles predicted the presence of FILD at HRCT (OR 13.46, 95% CI 5.85–30.96, p < 0.001) and most strongly the Usual Interstitial Pneumonia (UIP) pattern (OR 19.8, 95% CI 5.28–74.25, p < 0.001). Extent of isolated reticulation (OR 2.04, 95% CI 1.62–2.57, p < 0.001), honeycombing (OR 1.88, 95% CI 1.24–2.83, < 0.01), ground glass opacities (OR 1.74, 95% CI 1.29–2.32, p < 0.001) and traction bronchiectasis (OR 1.55, 95% CI 1.03–2.32, p < 0.05) were all independently associated with the presence of “Velcro-type” crackles.Conclusions“Velcro-type” crackles predict the presence of FILD and directly correlate with the extent of distinct radiologic features of pulmonary fibrosis. Such evidence provides grounds for further investigation of lung sounds as an early identification tool in FILD.

Clinical features, risk factors, and outcomes of patients with interstitial pneumonia with autoimmune features: a population-based study.

To investigate the clinical features, risk factors and outcomes of patients with interstitial pneumonia with autoimmune features (IPAF). A total of 1429 patients with idiopathic interstitial pneumonia (IIP) and undifferentiated connective tissue disease-associated interstitial lung disease (UCTD-ILD) were screened to identify patients who met IPAF criteria. Clinical, serological, and morphological features of patients with IPAF were characterized. Outcomes between patients with IPAF, UCTD-ILD, and IIP who were divided into idiopathic pulmonary fibrosis (IPF) and non-IPF groups were compared using survival as an endpoint. Patients with IPAF were much common in young female and had lower percentage of ever smoking and a significantly shorter survival than those with non-IPAF (P < 0.001). Subgroup analysis revealed that IPAF cohort survival was worse than that in non-IPF (P < 0.001), but better than that in IPF (P < 0.001). In IPAF cohort, the most common systemic symptom and serological abnormality were Raynaud's phenomenon (12.9%) and ANA ≥ 1:320 (49.2%); the most frequent high-resolution computed tomography (HRCT) pattern was nonspecific interstitial pneumonia (NSIP) (61.6%). Multivariate analysis indicated that several factors including age, smoking history, organizing pneumonia (OP) pattern in HRCT, and anti-RNP positivity were independently associated with significantly worse survival. IPAF had the distinct clinical features and outcomes compared with other groups of ILD. Additional studies should be needed to explore the underlying autoimmune mechanism and to determine risk stratification in future clinical research.

Radiological fibrosis score is strongly associated with worse survival in rheumatoid arthritis-related interstitial lung disease

Objectives: High-resolution computed tomography (HRCT) parenchymal patterns have been used to predict prognosis in patients with interstitial lung disease (ILD). In idiopathic pulmonary fibrosis, the fibrosis score (i.e. the combined extent of reticulation and honeycombing) has been associated with worse survival. This study aimed to identify HRCT patterns and patient characteristics that can predict poor prognosis in rheumatoid arthritis-related ILD (RA-ILD).Methods: We retrospectively analysed 65 patients with newly diagnosed RA-ILD from 2007 to 2016 at Kurashiki Central hospital. Using univariate and bivariate Cox regression analysis, associations with mortality, were identified.Results: During a median follow-up of 56.5 months, 16/65 (24.6%) patients died. Univariate analysis identified six significant poor prognostic factors: lower baseline % predicted forced vital capacity, total interstitial disease score, reticulation score, traction bronchiectasis score, fibrosis score, and definite UIP pattern. Fibrosis score remained to be an independently significant poor prognostic factor of survival on bivariate analysis. Patients with a fibrosis score >20% had higher mortality (HR, 9.019; 95% CI, 2.87–28.35; p < .05).Conclusion: This study showed that fibrosis score is strongly associated with worse survival in RA-ILD, and patients with fibrosis score >20% had a 9.019-fold increased risk of mortality.

Undifferentiated Connective Tissue Disease and Interstitial Lung Disease: Trying to Define Patterns

ObjectivesTo identify clinical or immunological features in patients with undifferentiated connective tissue disease (UCTD) associated interstitial lung disease (ILD), in order to group them and recognize different functional and high resolution computed tomography (HRCT) behavior. MethodsRetrospective cohort study. Patients meeting Kinder criteria for UCTD were included. We defined the following predictive variables: ‘highly specific’ connective tissue disease (CTD) manifestations (Raynaud's phenomenon, dry eyes or arthritis), high antinuclear antibody (ANA) titer (above 1:320), and ‘specific’ ANA staining patterns (centromere, cytoplasmic and nucleolar patterns). We evaluated the following outcomes: change in the percentage of the predicted forced vital capacity (FVC%) during the follow-up period, and HRCT pattern. ResultsSixty-six patients were included. Twenty-nine (43.94%) showed at least one ‘highly specific’ CTD manifestation, 16 (28.57%) had a ‘specific’ ANA staining pattern and 29 (43.94%) high ANA titer. Patients with ‘highly specific’ CTD manifestations were younger (mean [SD] 52 years [14.58] vs 62.08 years [9.46], P<.001), were more likely men (10.34% vs 48.65%, P<.001) and showed a smaller decline of the FVC% (median [interquartile range] 1% [−1 to 10] vs −6% [−16 to −4], P<.006). In the multivariate analysis, the presence of highly specific manifestations was associated with improvement in the FVC% (B coefficient of 13.25 [95% confidence interval, 2.41 to 24.09]). No association was observed in relation to the HRCT pattern. ConclusionThe presence of ‘highly specific’ CTD manifestations was associated with female sex, younger age and better functional behavior. These findings highlight the impact of the clinical features in the outcome of patients with UCTD ILD.

Practical Approach to the Evaluation and Management of Rheumatoid Arthritis-Interstitial Lung Disease Based on its Proven and Hypothetical Mechanisms.

The prevalence of interstitial lung disease in patients with rheumatoid arthritis varies from 10 to 42%. Rheumatoid arthritis patients with interstitial lung disease have three times the risk of death compared with those without the disease. Prognosis seems to be related to the high-resolution computed tomography pattern. Usual interstitial pneumonia pattern, resembling idiopathic pulmonary fibrosis, carries a worse prognosis. Validated strategies to identify different phenotypes and assess the disease activity in rheumatoid arthritis interstitial lung disease are lacking. However, the utilization of high-resolution computed tomography, composed disease activity scores, and anti-citrullinated peptide antibodies titers can help to guide decisions in clinical practice. Mechanisms involved in lung disease may be different from those implicated in joint involvement. This could explain why in a significant proportion of cases, interstitial lung disease does not improve or even worsens with standard therapies used successfully to treat the joint component (e.g. anti- umor necrosis factor agents). In this scenario, a group of drugs that targets the adaptive immune response (e.g. rituximab or abatacept) seems to target more specifically the process that takes place in the lungs. Moreover, the recent emergence of anti-fibrotic drugs, which have already proven effective in idiopathic pulmonary fibrosis, may provide an alternative treatment strategy in rheumatoid arthritis-usual interstitial pneumonia. In this review, we propose a practical approach to the evaluation and therapy of rheumatoid arthritis interstitial lung disease. Validation of strategies directed to assess the activity of lung disease and identify the underlying mechanisms are needed. Clinical trials evaluating a therapeutic approach with specific targets based on the disease phenotype are warranted.