Adjacent parenchymal abnormalities in peripheral bronchogenic carcinoma: correlation of thin-section CT with histology

Our purpose is to correlate thin section CT of peripheral bronchogenic carcinomas with histologically detected lymphatic or vascular invasion. Retrospective 3-year database search revealed 186 surgical resections for primary bronchogenic carcinoma, of which 58 had available preoperative imaging performed at our institution. Cases with prior surgery, nonconfirmatory pathology, remote imaging, or central location were excluded, resulting in a study population of 42 patients, 25 men, 17 women, with a mean age of 69 years. Imaging with 1-3 mm collimation was performed within a mean of 32 days prior to surgery. Histologic diagnoses included adenocarcinoma (n = 24, 57%), squamous cell carcinoma (n = 13, 31%), large cell carcinoma (n = 4, 10%), and small cell carcinoma (n = 1, 2%), with a mean tumor size of 27 mm. Three radiologists blindly and independently recorded bronchovascular thickening, septal and nonseptal opacities, and the extent of each beyond tumor margins: 1) <5 mm, 2) 5-10 mm, and 3) >10 mm. Lymphangio-invasion was correlated with imaging findings, tumor size, and histology. Adjacent parenchymal abnormalities were recorded in 40 (95%) of 42 masses, with isolated nonseptal opacities representing the most frequent abnormality in 21 (50%), followed by bronchovascular thickening in 16 (38%), and septal opacities in 12 (29%). Lymphangio-invasion was present in 16 (38%) of cases. The frequency of lymphangio-invasion was highest (53%) in cases with 2 or more positive findings, and extension beyond 10mm from the tumor margin. This trend did not achieve statistical significance by ROC analysis. Lymphangio-invasion was positively correlated with tumor size, P =.03, but not histology.In conclusion, parenchymal abnormalities beyond tumor margins shown by CT may be due to lymphangio-invasion but imaging findings did not reliably distinguish cases with and without lymphangio-invasion.     

Characteristics and disease activity of early interstitial lung disease in subjects with true parenchymal abnormalities in the posterior subpleural aspect of the lung

STUDY OBJECTIVES: To evaluate characteristics or disease activity of early interstitial lung disease (ILD) in subjects with true parenchymal abnormalities in the posterior subpleural aspect of the lung. PATIENTS AND METHODS: This study enrolled 14 subjects with dependent densities that disappeared on helical CT obtained with the subject prone (control group) and 7 subjects with true parenchymal abnormalities that remained unchanged on prone CT image but were not detectable on chest radiographs (true abnormalities group). Pulmonary function tests and serum markers for idiopathic lung fibrosis as KL-6, surfactant protein D (SP-D), and surfactant protein A (SP-A) in the two groups were evaluated. RESULTS: In the true abnormalities group, curvilinear subpleural lines or thickened interlobular and intralobular lines were observed more frequently in the lower lung fields. Diffusing capacities of the lung for carbon monoxide (15.3 +/- 3.5 mL/min/mm Hg vs 18.8 +/- 3.7 mL/min/mm Hg, p = 0.0493) were lower, and KL-6 (607 +/- 297 U/mL vs 318 +/- 143 U/mL, p = 0.0090), SP-A (59 +/- 24 ng/mL vs 34 +/- 12 ng/mL, p = 0.0207), and SP-D (112 +/- 54 ng/mL vs 42 +/- 24 ng/mL, p = 0.0028) were higher in the true abnormalities group than in the control group (+/- SD). CONCLUSION: True parenchymal abnormalities in the posterior subpleural aspect of the lung may indicate early ILD activity.     

Smoking-related diffuse parenchymal lung disease: HRCT-pathologic correlation

Response by the lung to inhaled cigarette smoke varies widely between individuals and ranges from subclinical respiratory bronchiolitis to end-stage Langerhans' cell histiocytosis. The variety of interstitial lung diseases associated with cigarette smoking is wider than generally appreciated, and these often coexist. An understanding of the pathological basis of smoking-related lung disease helps to explain the sometimes complex patterns encountered on high-resolution computed tomography (HRCT). The recent refinement of the classification of the idiopathic interstitial pneumonias and the longitudinal study of cigarette smokers with HRCT has furthered understanding of what should be regarded as an overlapping group of entities. In this article the individual interstitial diseases ascribable to cigarette smoking are discussed in terms of their pathology and corresponding HRCT signs. Emphasis is placed on the frequent coexistence of various forms of smoking-related interstitial lung disease.     

Nonspecific interstitial pneumonia associated with polymyositis and dermatomyositis: serial high-resolution CT findings and functional correlation

STUDY OBJECTIVES: We described the features seen on serial high-resolution CT scans of nonspecific interstitial pneumonia (NSIP) that was associated with polymyositis (PM) and dermatomyositis (DM), and we correlated the changes in the CT scan findings with those of pulmonary function test results. Design, setting and patients: Serial CT scans of 14 patients with histologically proven NSIP and PM/DM from two university hospitals were evaluated retrospectively (follow-up period, 3 to 61 months; mean follow-up period, 27.6 months). Using initial and follow-up CT scan findings, the extent of each type of opacity and the total area of increased opacity were calculated and correlated with the results of pulmonary function tests. MEASUREMENTS AND RESULTS: The predominant findings on the initial CT scans were of reticular and/or ground-glass opacities with or without consolidation. Reticular and ground-glass opacities predominated in the lower zone of each lung, and consolidation predominated at the lung periphery. Thirteen patients showed significant improvement of the total area of increased opacity (p < 0.05), and this decrease in extent inversely correlated with changes in FVC (r = -0.650; p = 0.031). Ground-glass and reticular opacities also were improved significantly in 11 and 13 patients, respectively. The decrease in the extent of ground-glass opacity correlated inversely with the changes in FVC (r = -0.758; p = 0.0119) and diffusion capacity for carbon monoxide (r = -0.669; p = 0.0448). In one patient, ground-glass opacity progressed, and death occurred after 3 months. Traction bronchiectasis was seen in 12 patients, and it improved in four patients after treatment. Honeycomb lung was not noted in any patient during follow-up. CONCLUSIONS: With treatment, serial CT scans of PM/DM patients with NSIP showed significant improvement in the abnormal opacities, and radiographic progression of lung fibrosis was limited. The CT scan features and clinical course of NSIP in PM/DM patients were relatively uniform, and this constitutes a subset of NSIP.     

Outcomes of patients with interstitial lung disease referred for lung transplant assessment

Background: Patients with interstitial lung disease (ILD) very frequently die before the opportunity to receive lung transplantation (LTx). This retrospective study describes the clinical course of 86 patients with ILD referred for LTx assessment between January 1999 and December 2002. Aims: (i) To describe the outcomes, (ii) to identify reasons of delay to transplantation, (iii) to describe the causes of death/complications and (iv) to assess the pathological diagnosis and concordance with explanted lung pathology. Methods: Data were collected from the case notes of all patients with ILD referred to the Alfred Hospital over a 4‐year period. Results: Twenty women and 66 men, mean age of 55 ± 8 years, were referred for LTx assessment. Forty‐five patients were deemed not suitable for LTx and 41 were listed. Twenty‐two patients underwent transplantation, 16 died on the waiting list and 7 are still on the waiting list. Complications were frequent (e.g. pulmonary embolism, malignancy and infection) and carried high mortality. Patients dying on the waiting list appeared generally to be in accelerated decline, dying shortly after listing, with no evidence in their lung function test assessment predicting them as a poor prognosis group. Conclusions: Serious complications and death on the waiting list of patients with idiopathic pulmonary fibrosis are high, not apparently because of delayed referral but usually in patients undergoing very rapid decline.     

Pre-existing interstitial lung abnormalities are risk factors for immune checkpoint inhibitor-induced interstitial lung disease in non-small cell lung cancer

BackgroundApproximately 5% of non-small cell lung cancer (NSCLC) patients develop immune checkpoint inhibitor (ICI)-induced interstitial lung disease (ICI-ILD), 10% of whom die. However, there are no established risk factors for its occurrence. Interstitial lung abnormalities (ILA) are areas of increased lung density on lung computed tomography (CT) in individuals with no known ILD. This study retrospectively investigated whether any patient characteristics, including ILA, were risk factors for ICI-ILD in patients with NSCLC.MethodsNSCLC patients who received anti-programmed death (PD)-1 antibody treatment at our hospital between September 2015 and December 2017 were enrolled. Information on patient characteristics before anti-PD-1 antibody administration, including chest CT findings and laboratory data, were obtained.ResultsAmong 83 enrolled patients, the incidence of ICI-ILD was 16.9% (14/83). All ICI-ILD cases developed by the third line of treatment. The incidence of ICI-ILD was significantly higher in patients with pre-existing ILA than that in those without (p = 0.007). Furthermore, patients with ground glass attenuation (GGA) in ILA had a higher incidence of ICI-ILD than that in those without (p < 0.001). In univariate logistic analysis, ILA were significant risk factors for ICI-ILD (p = 0.005). Multivariate logistic analysis revealed that only GGA in ILA was a significant risk factor for ICI-ILD (p < 0.001).ConclusionsPre-existing ILA are risk factors for ICI-ILD and GGA in ILA is an independent risk factor for ICI-ILD. Therefore, we should be more aware of the development of ICI-ILD in patients with ILA, especially those with GGA.     

High-resolution CT scan findings in patients with symptomatic scleroderma-related interstitial lung disease

BACKGROUND: Lung disease has become the leading cause of mortality and morbidity in scleroderma (SSc) patients. The frequency, nature, and progression of interstitial lung disease seen on high-resolution CT (HRCT) scans in patients with diffuse SSc (dcSSc) compared with those with limited SSc (lcSSc) has not been well characterized. METHODS: Baseline HRCT scan images of 162 participants randomized into a National Institutes of Health-funded clinical trial were compared to clinical features, pulmonary function test measures, and BAL fluid cellularity. The extent and distribution of interstitial lung disease HRCT findings, including pure ground-glass opacity (pGGO), pulmonary fibrosis (PF), and honeycomb cysts (HCs), were recorded in the upper, middle, and lower lung zones on baseline and follow-up CT scan studies. RESULTS: HRCT scan findings included 92.9% PF, 49.4% pGGO, and 37.2% HCs. There was a significantly higher incidence of HCs in the three zones in lcSSc patients compared to dcSSc patients (p = 0.034, p = 0.048, and p = 0.0007, respectively). The extent of PF seen on HRCT scans was significantly negatively correlated with FVC (r = - 0.22), diffusing capacity of the lung for carbon monoxide (r = - 0.44), and total lung capacity (r = - 0.36). A positive correlation was found between pGGO and the increased number of acute inflammatory cells found in BAL fluid (r = 0.28). In the placebo group, disease progression was assessed as 30% in the upper and middle lung zones, and 45% in the lower lung zones. No difference in the progression rate was seen between lcSSc and dcSSc patients. CONCLUSIONS: PF and GGO were the most common HRCT scan findings in symptomatic SSc patients. HCs were seen in more than one third of cases, being more common in lcSSc vs dcSSc. There was no relationship between progression and baseline PF extent or lcSSc vs dcSSc. Trial registration: Clinicaltrials.gov Identifier: NCT00004563.     

Clinical assessment for pulmonary hypertension in interstitial lung disease

Background

Pulmonary hypertension (PH) is an important complication of interstitial lung disease (ILD), as its development confers a poor prognosis. There are no specific recommendations for methods of assessment for PH in ILD populations.

Aims

To determine current assessment practices for PH in an Australian ILD centre.

Methods

In the Austin Health ILD database, 162 consecutive patients with idiopathic pulmonary fibrosis or connective tissue disease-associated ILD were identified and retrospectively evaluated for methods of PH assessment with transthoracic echocardiography (TTE), serum N-terminal pro-brain natriuretic peptide (NT-proBNP) and right heart catheterisation (RHC) in relation to patient demographic and physiological parameters.

Results

The median follow-up was 30 (14.4–56.4) months. At baseline, vital capacity was 80.0 ± 18.4% predicted, and diffusing capacity for carbon monoxide was 59.6 ± 15.2% predicted. Evaluation for PH was performed in 147 (90.7%) patients, among whom 105 (64.8%) had TTE performed at least once. At the initial TTE, 33.7% patients had high probability of PH, defined as RVSP >40 mmHg + RAp and/or right ventricular dysfunction. At the time of the most recent TTE, these criteria were met in 45 (52.3%) patients. Elevated serum NT-proBNP levels during the first year were observed in 47 (38.8%) patients. Only 14 (8.6%) patients had RHC.

Conclusion

Our institutional PH assessment practice in ILD demonstrates a substantial prevalence of probable PH at baseline. As new therapies emerge for the treatment of PH in ILD, well-defined screening practices are important in this population for early identification and optimal management.     

Predictors of airway and parenchymal lung abnormalities in patients with rheumatoid arthritis

Aim of the workTo investigate the frequency and types of pulmonary involvement using high resolution computed tomography (HRCT) and pulmonary function tests (PFTs) and to identify different disease parameters as predictors of lung involvement.Patients and MethodsOne hundred RA patients were recruited from El-Maadi Armed Forces Rheumatology clinic. Spirometry, plain X-ray chest, and HRCT were performed. Disease activity score (DAS28) and Larsen score were assessed.ResultsThey were 77 females and 23 males with a mean age of 55.7 ± 11.4 years and disease duration of 14.9 ± 6.8 years. Extra-articular manifestations included pleura-pulmonary involvement (33%), eye dryness (30%) and skin nodules (13%). PFTs showed abnormalities in 38%. X-ray chest abnormalities were found in 12 patients as follows: pleural effusion (3%), atelectasis in (6%), pulmonary nodules (2%) and hyperinflated chest (3%). Abnormal HRCT findings were found in 68% of the patients: ground glass opacity (GGO) in 36 (52.9%), air trapping in 26 (38.2%), thickened septal/non-septal lines in 21 (30.9%), nodules in 17 (25%), Caplan’s syndrome in 8 (11.8%) and bronchial wall thickening in 8 (11.8%) while 3 (4.4%) showed honey combing and bronchiectasis. Passive smoking, chronic cough, Larsen score and anti-cyclic citrullinated peptide (anti-CCP) titre were significant predictors of lung involvement as detected by HRCT.ConclusionHRCT of the chest was found to be a more sensitive measure than spirometry to diagnose pulmonary abnormalities. Passive smoking, chronic cough, disease severity and high anti-CCP titre were significant independent predictors of lung involvement as detected by PFT and HRCT among rheumatoid patients.     

A case of idiopathic interstitial pneumonia with pneumothorax and pneumomediastinum, accompanied by rapid progression of cystic changes on CT

A case of idiopathic interstitial pneumonia (IIP) with pneumothorax and pneumomediastinum was presented. A 52-year-old male was admitted with the complaint of cough, fever and dyspnea. Chest roentgenogram revealed bilateral reticulonodular shadow and right pneumothorax. Radiological, laboratory and clinical findings were consistent with the diagnosis of acute exacerbation of IIP. Repeated chest CTs showed diffuse interstitial opacities and the presence of pneumothorax and pneumomediastinum. Furthermore, honeycombing and bullous change progressed markedly for two months. The mechanisms of pneumothorax and pneumomediastinum were speculated to be due to the rupture of those cystic lesions which had grown rapidly on follow-up CTs. It was suggested that the formation of honeycombing occurred within a few months and the increasing of honeycombing might be accompanied by so-called acute exacerbation of IIP. We propose that follow-up CTs were useful for the chronological study for interstitial lesions of IIP.     

RA-ILD与临床和实验室指标相关性研究

目的收集类风湿关节炎合并肺间质病变(RA-ILD)患者的相关临床指标、实验室指标和肺部影像学表现等临床资料,分析这些因素与RA-ILD的发生和发展的关系,为RA-ILD的诊疗提供一定的临床依据。方法回顾性收集2014年1月-2015年1月在新疆维吾尔自治区人民医院风湿免疫科住院的RA患者,一般资料、临床表现、实验室指标和影像学检查。结果 1 204例RA患者中44例发生ILD,占21.6%。6例胸闷、气短;6例有咳嗽、咳痰;6例听诊有Velcro音。比较发现RA-ILD组咳嗽咳痰、胸闷气短、Velcro音的发生率高于单纯RA组(P0.05)。RA-ILD组患者肺HRCT最常见的表现是磨玻璃影。2 RA-ILD组的平均病程、年龄明显大于单纯RA组(P0.05)。3 RA-ILD组白细胞、血红蛋白、血小板、DAS28、ESR、CRP、C3、C4、RF、GPI较单纯RA组差异无统计学意义(P0.05)。4 RA-ILD组抗CCP抗体滴度显著大于单纯RA组(P0.05)。5比较两组AKA阳性率差异有统计学意义(P0.05),而抗SSA抗体阳性率、抗核抗体阳性率差异无统计学意义(P0.05)。结论 RA-ILD患者年龄大、平均病程长,大部分临床表现不明显,需及时完善HRCT,早期诊断和治疗。高抗CCP抗体滴度、ANA阳性可能与RA-ILD的发生相关。     

Counting parenchymal cells in the goat lung with serial section reconstruction and stereology

Information about numbers of cells is needed to interpret cellular and tissue responses to injury. As a first step towards identifying changes in cell number and structure in injured lungs, this study reports the frequencies of 4 parenchymal cell types in the normal goat lung. Cells were counted using serial section reconstruction and light microscopy. Relative cell frequencies were (mean +/- standard error): type I cells (5.47 +/- 0.52%), type II cells 10.74 +/- 1.17%), capillary endothelial cells (47.50 +/- 1.42%), and interstitial cells (37.14 +/- 3.00%). These cell counts coming from serial section reconstructions allowed us to estimate mean nuclear diameters of the 4 cell types without assumptions for size, shape, and frequency distribution, and they were also used to evaluate counts of nuclear profiles taken from light and electron micrographs. When the same mean nuclear diameter was used, the counts of nuclear profiles from both light and electron microscopy gave similar stereological estimates for cell numbers, provided section compression was corrected. We conclude that lung parenchymal cells can be counted using light microscopy and serial section reconstruction and that this information provides a standard for evaluating stereological estimates of cell numbers.     

Linking parenchymal disease progression to changes in lung mechanical function by percolation

RATIONALE: The mechanical dysfunction accompanying parenchymal diseases such as pulmonary fibrosis and emphysema may follow a different course from the progression of the underlying microscopic pathophysiology itself, particularly in the early stages. It is tempting to speculate that this may reflect the geographical nature of lung pathology. However, merely ascribing mechanical dysfunction of the parenchyma to the vagaries of lesional organization is unhelpful without some understanding of how the two are linked. OBJECTIVES: We attempt to forge such a link through a concept known as percolation, which has been invoked to account for numerous natural processes involving transmission of events across complex networks. METHODS: We numerically determined the bulk stiffness (corresponding to the inverse of lung compliance) of a network of springs representing the lung parenchyma. We simulated the development of fibrosis by randomly stiffening individual springs in the network, and the development of emphysema by preferentially cutting springs under the greatest tension. MEASUREMENTS AND MAIN RESULTS: When the number of stiff springs was increased to the point that they suddenly became connected across the network, the model developed a sharp increase in its bulk modulus. Conversely, when the cut springs became sufficiently numerous, the elasticity of the network fell to zero. These two conditions represent percolation thresholds that we show are mirrored structurally in both tissue pathology and macroscopic computed tomography images of human idiopathic fibrosis and emphysema. CONCLUSIONS: The concept of percolation may explain why the development of symptoms related to lung function and the development of parenchymal pathology often do not progress together.