Deep-Learning Reconstruction of High-Resolution CT Improves Interobserver Agreement for the Evaluation of Pulmonary Fibrosis.

Objective: This study aimed to investigate whether deep-learning reconstruction (DLR) improves interobserver agreement in the evaluation of honeycombing for patients with interstitial lung disease (ILD) who underwent high-resolution computed tomography (CT) compared with hybrid iterative reconstruction (HIR). Methods: In this retrospective study, 35 consecutive patients suspected of ILD who underwent CT including the chest region were included. High-resolution CT images of the unilateral lung with DLR and HIR were reconstructed for the right and left lungs. A radiologist placed regions of interest on the lung and measured standard deviation of CT attenuation (i.e., quantitative image noise). In the qualitative image analyses, 5 blinded readers assessed the presence of honeycombing and reticulation, qualitative image noise, artifacts, and overall image quality using a 5-point scale (except for artifacts which was evaluated using a 3-point scale). Results: The quantitative and qualitative image noise in DLR was remarkably reduced compared to that in HIR (P < .001). Artifacts and overall DLR quality were significantly improved compared to those of HIR (P < .001 for 4 out of 5 readers). Interobserver agreement in the evaluations of honeycombing and reticulation for DLR (0.557 [0.450-0.693] and 0.525 [0.470-0.541], respectively) were higher than those for HIR (0.321 [0.211-0.520] and 0.470 [0.354-0.533], respectively). A statistically significant difference was found for honeycombing (P = .014). Conclusions: DLR improved interobserver agreement in the evaluation of honeycombing in patients with ILD on CT compared to HIR.

Narrowing the Differential Diagnosis of Cystic Lesions in Smokers with Expiratory CT Acquisition Using the Cyst-Airway Communication Hypothesis.

The aim of this study was to assess percentage respiratory changes (δ) in the size of pulmonary cysts of different smoking-related etiologies. Retrospectively, we measured the cystic lesions due to histopathological-confirmed honeycombing from interstitial pulmonary fibrosis, pulmonary Langerhans cell histiocytosis (PLCH), and paraseptal emphysema, using paired inspiratory and expiratory CT scans. In a sample of 72 patients and 216 lesions, the mean diameter of PLCH and honeycombing decreased during expiration (PLCH, δ = 60.9%; p = 0.001; honeycombing, δ = 47.5%; p = 0.014). Conversely, paraseptal emphysema did not show any changes (δ = 5.2%; p = 0.34). In summary, our results demonstrated that cysts in smokers with PLCH and honeycombing fibrosis get smaller during expiratory CT scans, whereas the size of cystic-like lesions due to paraseptal emphysema and bullae tend to remain constant during respiratory cycles. These results support the hypothesis of cyst-airway communication in some cystic diseases, which could assist in the differential diagnosis in smoking-related lung diseases.

[Chest high-resolution CT features analysis in predicting the progression of asbestosis].

Objective: To analyze the radiological characteristics of chest high-resolution computed tomography (HRCT) of patients with asbestosis, and to investigate the signs of predicting the disease progression of asbestosis. Methods: A prospective method was used to enroll 68 patients with asbestosis who were regularly followed up from 2013 to 2016. The radiological characteristics of patients with asbestosis were described by the International Classification of HRCT for Occupational and Environmental Respiratory Diseases (ICOERD) , and the differences between patients with and without progression were compared during the observation period. The Cox proportional hazards regression model was used to analyze the chest HRCT radiological signs predicting the progression of asbestosis. Results: The study included 68 patients with asbestosis aged (65.5±7.8) years old, of which 64.7% (44/68) were female, 29.4% (20/68) had a history of smoking. There was no significant difference in age, sex, smoking and asbestos exposure between patients with progressive asbestosis (20.6%, 14/68) and patients without progressive asbestosis (79.4%, 54/68) (P>0.05) . Chest HRCT of patients with asbestosis showed irregular and/or linear opacities, of which 5.9% (4/68) were accompanied by honeycombing. Irregular and/or linear opacities were mainly lower lung preponderant, often accompanied with ground glass opacity and mosaic perfusion. 98.5% (67/68) had pleural abnormalities, of which 39.7% (27/68) had diffuse pleural thickening with parenchymal bands and/or rounded atelectasis. The analysis of multivariable Cox proportional hazard regression showed that the risk of the progression of asbestosis was increased with higher irregular and/or linears opacities cores (HR=1.184, 95%CI: 1.012-1.384, P=0.034) and the appearance of honeycombing (HR=6.488, 95%CI: 1.447-29.097, P=0.015) . Conclusion: The irregular and/or linear opacities scores and honeycombing on chest HRCT are independent influencing factors for predicting the disease progression of asbestosis.

Impact of radiological honeycombing in rheumatoid arthritis-associated interstitial lung disease.

BACKGROUND: Interstitial lung disease (ILD) is the most common and important pulmonary manifestation of rheumatoid arthritis (RA). A radiological honeycomb pattern has been described in diverse forms of ILD that can impact survival. However, the clinical course and sequential radiological changes in the formation of the honeycomb pattern in patients with RA-ILD is not fully understood. METHODS: We evaluated the sequential changes in computed tomography findings in 40 patients with chronic forms of RA-ILD without the honeycomb pattern at initial diagnosis. We classified the patients into the Non-honeycomb group and Honeycomb group, and then analyzed the characteristics and prognosis of the two groups. The term "honeycomb formation" indicated a positive finding of honeycombing on any available follow-up CT. RESULTS: Our RA-ILD cohort included patients with probable usual interstitial pneumonia (UIP) (35%), nonspecific interstitial pneumonia (NSIP) (20%), and mixed NSIP/UIP (45%). Among all RA-ILD patients, 16 (40%) showed honeycomb formation on follow-up CT (median time between initial and last follow-up CT was 4.7 years). Patient characteristics and prognosis were not significantly different between the Non-honeycomb and Honeycomb groups. However, Kaplan-Meier survival curve for the time from the date of honeycomb formation to death showed a poor median survival time of 3.2 years. CONCLUSIONS: A certain number of patients with RA-ILD developed a honeycomb pattern during long-term follow-up, regardless of whether they had UIP or NSIP. Prognosis in the patients with characteristics of both progressive ILD and honeycomb formation could be poor. Although radiological findings over the disease course and clinical disease behavior in RA-ILD are heterogenous, clinicians should be alert to the possibility of progressive disease and poor prognosis in patients with RA-ILD who form a honeycomb pattern during follow-up observation.

Relationship of flow-volume curve pattern on pulmonary function test with clinical and radiological features in idiopathic pulmonary fibrosis.

BACKGROUND: The flow-volume (FV) curve pattern in the pulmonary function test (PFT) for obstructive lung diseases is widely recognized. However, there are few reports on FV curve pattern in idiopathic pulmonary fibrosis (IPF). In this study, we investigated the relationship between FV curve pattern and clinical or radiological features in IPF. METHODS: The FV curves on PFTs and chest high-resolution computed tomography (HRCT) images of 130 patients with IPF were retrospectively evaluated. The FV curves were divided into four groups based on the presence or absence of the convex and concave patterns: convex/concave, non-convex/concave, convex/non-concave, and non-convex/non-concave. Using a computer-aided system, CT honeycombing area (%HA) and subtracted low attenuation area (%sLAA) were quantitatively measured. To assess the distribution of CT findings, the lung area was divided into upper, lower, central, and peripheral areas. The relationships of FV curve patterns with patient characteristics, spirometry results, and quantitative CT findings were evaluated. RESULTS: The patients with convex pattern was identified in 93 (71.5%) and concave pattern in 72 (55.4%). Among the four groups, patients with the convex/non-concave pattern had significantly lower forced vital capacity (FVC) and higher %HA of the upper/peripheral lung area (p = 0.018, and p = 0.005, respectively). The convex/non-concave pattern was a significant predictor of mortality for IPF (hazard ratio, 2.19; p = 0.032). CONCLUSIONS: Patients with convex/non-concave pattern in FV curve have lower FVC and poorer prognosis with distinct distribution of fibrosis. Hence, FV curve pattern might be a useful predictor of mortality in IPF.

Implications of the diagnostic criteria of idiopathic pulmonary fibrosis in clinical practice: Analysis from the Australian Idiopathic Pulmonary Fibrosis Registry.

BACKGROUND AND OBJECTIVE: Current guidelines for the diagnosis of idiopathic pulmonary fibrosis (IPF) provide specific criteria for diagnosis in the setting of multidisciplinary discussion (MDD). We evaluate the utility and reproducibility of these diagnostic guidelines, using clinical data from the Australian IPF Registry. METHODS: All patients enrolled in the registry undergo a diagnostic review whereby international IPF guidelines are applied via a registry MDD. We investigated the clinical applicability of these guidelines with regard to: (i) adherence to guidelines, (ii) Natural history of IPF diagnostic categories and (iii) Concordance for diagnostic features. RESULTS: A total of 417 participants (69% male, 70.6 ± 8.0 years) with a clinical diagnosis of IPF underwent MDD. The 23% of participants who did not meet IPF diagnostic criteria displayed identical disease behaviour to those with confirmed IPF. Honeycombing on radiology was associated with a worse prognosis and this translated into poorer prognosis in the 'definite' IPF group. While there was moderate agreement for IPF diagnostic categories, agreement for specific radiological features, other than honeycombing, was poor. CONCLUSION: In clinical practice, physicians do not always follow IPF diagnostic guidelines. We demonstrate a cohort of IPF patients who do not meet IPF diagnostic guideline criteria, based largely on their radiology and lack of lung biopsy, but who have outcomes identical to those with IPF.

The acoustic characteristics of fine crackles predict honeycombing on high-resolution computed tomography.

BACKGROUND: Honeycombing on high-resolution computed tomography (HRCT) is a distinguishing feature of usual interstitial pneumonia and predictive of poor outcome in interstitial lung diseases (ILDs). Although fine crackles are common in ILD patients, the relationship between their acoustic features and honeycombing on HRCT has not been well characterized. METHODS: Lung sounds were digitally recorded from 71 patients with fine crackles and ILD findings on chest HRCT. Lung sounds were analyzed by fast Fourier analysis using a sound spectrometer (Easy-LSA; Fukuoka, Japan). The relationships between the acoustic features of fine crackles in inspiration phases (onset timing, number, frequency parameters, and time-expanded waveform parameters) and honeycombing in HRCT were investigated using multivariate logistic regression analysis. RESULTS: On analysis, the presence of honeycombing on HRCT was independently associated with onset timing (early vs. not early period; odds ratios [OR] 10.407, 95% confidence interval [95% CI] 1.366-79.298, P = 0.024), F99 value (the percentile frequency below which 99% of the total signal power is accumulated) (unit Hz = 100; OR 5.953, 95% CI 1.221-28.317, P = 0.029), and number of fine crackles in the inspiratory phase (unit number = 5; OR 4.256, 95% CI 1.098-16.507, P = 0.036). In the receiver-operating characteristic curves for number of crackles and F99 value, the cutoff levels for predicting the presence of honeycombing on HRCT were calculated as 13.2 (area under the curve [AUC], 0.913; sensitivity, 95.8%; specificity, 75.6%) and 752 Hz (AUC, 0.911; sensitivity, 91.7%; specificity, 85.2%), respectively. The multivariate logistic regression analysis additionally using these cutoff values revealed an independent association of number of fine crackles in the inspiratory phase, F99 value, and onset timing with the presence of honeycombing (OR 33.907, 95% CI 2.576-446.337, P = 0.007; OR 19.397, 95% CI 2.311-162.813, P = 0.006; and OR 12.383, 95% CI 1.443-106.293, P = 0.022; respectively). CONCLUSIONS: The acoustic properties of fine crackles distinguish the honeycombing from the non-honeycombing group. Furthermore, onset timing, number of crackles in the inspiratory phase, and F99 value of fine crackles were independently associated with the presence of honeycombing on HRCT. Thus, auscultation routinely performed in clinical settings combined with a respiratory sound analysis may be predictive of the presence of honeycombing on HRCT.

Effect of Nintedanib in Subgroups of Idiopathic Pulmonary Fibrosis by Diagnostic Criteria.

RATIONALE: In the absence of a surgical lung biopsy, patients diagnosed with idiopathic pulmonary fibrosis (IPF) in clinical practice could participate in the INPULSIS trials of nintedanib if they had honeycombing and/or traction bronchiectasis plus reticulation, without atypical features of usual interstitial pneumonia (UIP), on high-resolution computed tomography (HRCT). Thus, the patients in these trials represented patients with definite UIP and a large subgroup of patients with possible UIP. OBJECTIVES: To investigate the potential impact of diagnostic subgroups on the progression of IPF and the effect of nintedanib. METHODS: We conducted a post hoc subgroup analysis of patients with honeycombing on HRCT and/or confirmation of UIP by biopsy versus patients without either, using pooled data from the INPULSIS trials. MEASUREMENTS AND MAIN RESULTS: Seven hundred twenty-three (68.1%) patients had honeycombing and/or biopsy, and 338 (31.9%) patients had no honeycombing or biopsy. In these subgroups, respectively, the adjusted annual rate of decline in FVC in patients treated with placebo was -225.7 and -221.0 ml/yr, and the nintedanib versus placebo difference in the adjusted annual rate of decline in FVC was 117.0 ml/yr (95% confidence interval, 76.3-157.8) and 98.9 ml/yr (95% confidence interval, 36.4-161.5). There was no significant treatment-by-subgroup interaction (P = 0.8139). Adverse events were similar between the subgroups. CONCLUSIONS: Patients with IPF diagnosed in clinical practice who had possible UIP with traction bronchiectasis on HRCT and had not undergone surgical lung biopsy had disease that progressed in a similar way, and responded similarly to nintedanib, to that of patients with honeycombing on HRCT and/or confirmation of UIP by biopsy.

Confluent fibrosis and fibroblast foci in fibrotic non-specific interstitial pneumonia.

AIMS: The separation of fibrotic non-specific interstitial pneumonia (FNSIP) and usual interstitial pneumonia (UIP) is important for patient treatment and prognosis, but is sometimes a difficult diagnostic problem. Most authors believe that fibroblast foci are rare in NSIP, and that the finding of multiple fibroblast foci suggests a diagnosis of UIP. Similarly, architectural distortion is viewed as favouring a diagnosis of UIP. This study aims to assess these criteria for their diagnostic utility. METHODS AND RESULTS: We report eight patients with a high-resolution computed tomography diagnosis of FNSIP, and a picture of fibrotic NSIP on biopsy, but in whom, in all cases, fibrosis focally widened the walls to the point of confluence, producing architectural distortion in the form of variably sized, sometimes quite large, blocks of fibrosis, but not honeycombing. Fibroblast foci varied from four to nine per section, and point counting morphometry showed that the areas containing large blocks of confluent fibrosis were geographically strongly associated with fibroblast foci, whereas fibroblast foci were rare away from the confluent fibrosis. Follow-up imaging studies (mean interval 19.5 months; range 2-42 months) in six patients revealed stable or improved disease in four and worsening disease in two. No case had or developed radiological honeycombing, and there were no other imaging findings to suggest a diagnosis of UIP. CONCLUSIONS: Otherwise typical FNSIP cases can show architectural distortion caused by confluence or marked expansion of fibrotic alveolar walls. These areas tend to be associated with fibroblast foci. These findings do not imply a poor prognosis, and should not be confused with UIP.

JOURNAL CLUB: Evidence of Interstitial Lung Disease on Low-Dose Chest CT Images: Prevalence, Patterns, and Progression.

OBJECTIVE: The purposes of this study were to determine the prevalence of interstitial lung disease (ILD) in a cohort undergoing low-dose CT screening for lung cancer, to identify the CT patterns of fibrosis, and to determine prognostic factors of disease progression. MATERIALS AND METHODS: The study drew from a database of 951 participants in a lung cancer screening program between 2010 and 2014. Three thoracic radiologists reviewed CT scans to identify the ILD findings, defined as traction bronchiectasis, ground-glass opacities with traction bronchiectasis, reticulations with traction bronchiectasis, and honeycombing. Evidence of ILD was considered present if at least two of three reviewing radiologists agreed. Age, smoking history, and CT evidence of emphysema were also documented. RESULTS: Of the 951 participants, 63 (6.6%) had CT evidence of ILD, and 16 of the 63 (1.7% of the total cohort) had honeycombing. Significant univariate predictors of ILD were male sex (p = 0.003), older age (p < 0.0001), higher number of pack-years of cigarette smoking (p = 0.0003), and greater severity of emphysema (p = 0.004), but only age and male sex remained significant in the multivariate analysis. The most common pattern of ILD was peripheral fibrosis without honeycombing involving multiple lobes. The presence of honeycombing was significantly associated with progression of fibrosis score (p = 0.0001) and extent of fibrosis (p = 0.005). CONCLUSION: A potential added benefit of CT screening is earlier diagnosis of ILD in older smokers, who are at increased risk. Radiologists should recognize the earliest findings of ILD and understand the importance of early recognition.

From "traction bronchiectasis" to honeycombing in idiopathic pulmonary fibrosis: A spectrum of bronchiolar remodeling also in radiology?

BACKGROUND: The diagnostic and prognostic impact of traction bronchiectasis on high resolution CT scan (HRCT) in patients suspected to have idiopathic pulmonary fibrosis (IPF) is increasing significantly. MAIN BODY: Recent data demonstrated that cysts in honeycombing areas are covered by epithelium expressing bronchiolar markers. In IPF bronchiolization is the final consequence of a variety of pathogenic events starting from alveolar stem cell exhaustion, and ending in a abnormal/dysplastic proliferation of bronchiolar epithelium. CT scan features of traction bronchiectasis and honeycombing should be interpreted under the light of these new pathogenetic and morphologic considerations. SHORT CONCLUSION: We suggest that in IPF subjects traction bronchiectasis and honeycombing -now defined as distinct entities on HRCT scan- are actually diverse aspects of a continuous spectrum of lung remodeling.

"Bubbly lung", a honeycombing variant with more favorable outcome.

BACKGROUND: Although radiologic honeycombing is generally associated with progressive fibrosis and a dismal prognosis, some patients display an unexpectedly indolent clinical course. We aimed to assess for variants of honeycombing associated with a more favorable prognosis. METHODS: A computer-assisted search was conducted to identify patients encountered at Mayo Clinic from 1998 to 2022 who had undergone chest CT that manifested exuberant honeycombing. Medical records and chest imaging studies were reviewed to identify clinical, pulmonary function and radiologic features. RESULTS: Among 136 patients with exuberant honeycombing, 23 patients were identified with CT features of what we termed "bubbly lung" characterized by extensive macrocystic fibrosis; 17 (74%) were female with a median age of 71 years (range, 32-88) at baseline. Underlying diagnoses were ANCA associated vasculitis (22%), overlap CTD (22%), rheumatoid arthritis (17%), IPF (17%), IPAF (9%), systemic sclerosis (4%), undifferentiated CTD (4%), and dermatomyositis (4%). Median FVC was 78% predicted (range 35-112), median DLco was 41% predicted (range 10-92), and median TLC was 73% predicted (range 57-116). Serial FVC measurements were available for 19 (83%) patients with a median interval of 4.7 years (range: 0.4-20); median FVC change per year was 23 ml (range -279 to +232) and median FVC % predicted change per year was 0.00% (range -3.20 to +6.79%). The median survival was 7.1 years, 5-year survival was 76% (95% CI: 58%-100%) and 10-year survival was 48%. CONCLUSIONS: "Bubbly lung" is a variant of exuberant honeycombing that is associated with better-than-expected outcome and FVC decline per year.

Update on Interstitial Pneumonias.

The American Thoracic Society/European Respiratory Society/Japanese Respiratory Society/Asociación Latinoamericana de Tórax 2018 clinical practice guideline and 2022 update provide recommendations to define and diagnose idiopathic pulmonary fibrosis (IPF) in patients with newly diagnosed interstitial lung disease. The guideline emphasizes recognition of usual interstitial pneumonia (UIP) and probable UIP patterns of fibrosis on high-resolution CT, which can obviate the need for surgical lung biopsy and allow timely initiation of antifibrotic pharmacotherapy citing a high correlation with UIP on histopathology. This article reviews the recent 2022 IPF clinical practice guideline with a focus on the imaging updates.

Hermansky-Pudlak Syndrome: A Rare Congenital Disorder With Interstitial Lung Disease.

Hermansky-Pudlak syndrome (HPS) is a genetic multisystemic disorder with oculocutaneous albinism, granulomatous colitis, bleeding diathesis, and pulmonary fibrosis. Multiple subtypes of HPS exist, with certain types having higher predilection for pulmonary fibrosis. This case report focuses on the demonstration of pulmonary imaging findings seen in a patient. Several imaging features overlap with idiopathic pulmonary fibrosis including traction bronchiectasis, pleural and peribronchovascular thickening, and reticulations. This case report highlights the differences seen in lung disease associated with HPS compared to other interstitial lung diseases, in addition to the multi-systemic features of HPS.

High-Resolution CT Scan Fibrotic Patterns in Stage IV Pulmonary Sarcoidosis: Impact on Pulmonary Function and Survival.

BACKGROUND: Different patterns of fibrosis on high-resolution CT scans (HRCT) have been associated with reduced survival in some interstitial lung diseases. Nothing is known about HRCT scan patterns and survival in sarcoidosis. RESEARCH QUESTION: Will a detailed description of the extent and pattern of HRCT scan fibrosis in patients with stage IV pulmonary sarcoidosis impact pulmonary function and survival? STUDY DESIGN AND METHODS: Two hundred forty patients with stage IV sarcoidosis at two large tertiary institutions were studied. The earliest HRCT scan with fibrosis was reviewed for extent of fibrosis (< 10%, 10%-20%, and > 20%) and presence of bronchiectasis, upper lobe fibrocystic changes, basal subpleural honeycombing, ground-glass opacities (GGOs), large bullae, and mycetomas. Presence of sarcoidosis-associated pulmonary hypertension (SAPH) and pulmonary function testing performed within 1 year of HRCT were recorded. Patients were followed up until last clinic visit, death, or lung transplantation. RESULTS: The mean age was 58.4 years. Seventy-four percent were Black, 63% were female, and mean follow-up was 7.4 years. Death or LT occurred in 53 patients (22%). Thirty-one percent had > 20% fibrosis, 25% had 10%-20% fibrosis, and 44% had < 10% fibrosis. The most common HRCT abnormalities were bronchiectasis (76%), upper lobe fibrocystic changes (36%), and GGOs (28%). Twelve percent had basal subpleural honeycombing, and 32% had SAPH. Patients with > 20% fibrosis had more severe pulmonary impairment, were more likely to have SAPH (53%), and had worse survival (44% mortality; P < .001). Upper lobe fibrocystic changes, basal subpleural honeycombing, and large bullae were associated with worse pulmonary function and worse survival. Patients with basal subpleural honeycombing had the worst pulmonary function and survival (55% mortality; P < .001). GGOs were associated with worse pulmonary function but not worse survival, and mycetomas were associated with worse survival but not worse pulmonary function. A Cox proportional hazards model indicated that basal subpleural honeycombing (hazard ratio, 7.95), diffusion capacity for carbon monoxide < 40% (HR, 5.67) and White race (hazard ratio, 2.61) were independent predictors of reduced survival. INTERPRETATION: HRCT scan features of fibrotic pulmonary sarcoidosis had an impact on pulmonary function and survival. Presence of >20% fibrosis and basal subpleural honeycombing are predictive of worse pulmonary function and worse survival in patients with stage IV pulmonary sarcoidosis.

Prevalence and prognostic meaning of interstitial lung abnormalities in remote CT scans of patients with interstitial lung disease treated with antifibrotic therapy.

OBJECTIVES: To describe the prevalence and characteristics of interstitial lung abnormalities (ILA) in CT scans performed prior to the initiation of antifibrotics in a series of patients with interstitial lung disease (ILD), and to identify characteristics apparent on early CT scans that could help to predict outcomes. METHODS: We conducted a retrospective observational study. The original cohort consisted of 101 patients diagnosed with ILD and treated with antifibrotics in a tertiary hospital. Patients were included if they had a thoracic CT scan performed at least one year before initiation of therapy. They were classified radiologically in three groups: without ILA, with radiological ILA and extensive abnormalities. ILA were classified as subpleural fibrotic, subpleural non-fibrotic and non-subpleural. The initial scan and the latest CT scan performed before treatment were read for assessing progression. The relationship between CT findings of fibrosis and the radiological progression rate and mortality were analyzed. RESULTS: We included 50 patients. Only 1 (2%) had a normal CT scan, 25 (50%) had extensive alterations and 24 (48%) had radiological criteria for ILA, a median of 98.2 months before initiation of antifibrotics, of them 18 (75%) had a subpleural fibrotic pattern. Significant bronchiectasis and obvious honeycombing in the lower zones were associated with shorter survival (p = 0.04). Obvious honeycombing in the lower zones was also significantly (p < 0.05) associated with a faster progression rate. CONCLUSIONS: Fibrotic ILAs are frequent in remote scans of patients with clinically relevant ILD, long before they require antifibrotics. Findings of traction bronchiectasis and honeycombing in the earliest scans, even in asymptomatic patients, are related to mortality and progression later on.

CANNOT B UIP.

The American Thoracic Society provides guidelines for the confident radiographic diagnosis of UIP. In addition, the guidelines identify findings on CT scans that should suggest an alternative diagnosis to UIP. These findings include consolidation, air trapping, nodules, ground glass opacities, cysts, and upper lung and bronchovascular distribution. We present a mnemonic to help the reader remember the list of findings that are inconsistent with UIP and provide imaging examples for completeness. The mnemonic is "CANNOT B" UIP.

Juvenile idiopathic arthritis presenting as diffuse alveolar hemorrhage at onset: A case series.

OBJECTIVE: The etiology of diffuse alveolar hemorrhage (DAH) in childhood is often unknown, and it may be an early manifestation of rheumatic disease. Juvenile idiopathic arthritis (JIA) is one of the most common rheumatic diseases in children, but DAH as an onset manifestation of JIA is rare. This study summarizes the clinical characteristics of patients with JIA presenting as DAH. METHODS: We retrospectively analyzed the age of onset, clinical manifestations, imaging features, treatments, and prognosis of five cases of JIA presenting as DAH. RESULTS: Themedian age at DAH onset was 6 months (range, 2 months-3 years). Pallor was the most common manifestation of onset (5/5). Other symptoms included cough (2/5), tachypnea (2/5), hemoptysis (1/5), cyanosis (1/5), and fatigue (1/5). Imaging showed ground-glass opacity (GGO) (5/5), subpleural or intrapulmonary honeycombing (4/5), consolidation (3/5), interlobular septal thickening (2/5), and nodules (1/5). Anticitrullinated protein antibodies (ACPA) and rheumatoid factor (RF) were positive in five children (5/5), and antinuclear antibody (ANA) was positive in four children (4/5). ANA in three children and ACPA/RF in one child were positive before the onset of joint symptoms. The median age at the onset of joint symptoms was 3 years and 9 months (2 years and 6 months-8 years). Joint symptoms were mainly characterized by joint swelling, pain, and difficulty walking, and the most commonly affected joints were the knees, ankles, and wrists. After the diagnosis of DAH, the five patients were treated with glucocorticoids. Alveolar hemorrhage was effectively controlled in three cases, but the other two patients still had anemia and poor improvements in chest imaging. After joint symptoms, the patients were treated with glucocorticoids combined with diclofenac, disease-modifying antirheumatic drugs, and biological agents. Alveolar hemorrhage was in remission, and joint symptoms were relieved in the five cases. CONCLUSION: DAH can be the first clinical manifestation of JIA, and joint involvement occurs 1-5 years later. Children with DAH who are positive for RF, ACPA, and/or ANA and have GGO accompanied by honeycombing on imaging should be concerned about their joint involvement in future.

Honeycomb lung is a major risk factor for preoperative radiological tumor size underestimation in patients with primary lung cancer.

Background: Lung cancer frequently occurs in lungs with background idiopathic interstitial pneumonias (IIPs). Limited resection is often selected to treat lung cancer in patients with IIPs in whom respiratory function is already compromised. However, accurate surgical margins are essential for curative resection; underestimating these margins is a risk for residual lung cancer after surgery. We aimed to investigate the findings of lung fields adjacent to cancer segments affect the estimation of tumor size on computed tomography compared with the pathological specimen. Methods: This analytical observational study retrospectively investigated 896 patients with lung cancer operated on at Fujita Health University from January 2015 to June 2020. The definition of underestimation was a ≥10 mm difference between the radiological and pathological maximum sizes of the tumor. Results: The lung tumors were in 15 honeycomb, 30 reticulated, 207 emphysematous, and 628 normal lungs. The ratio of underestimation in honeycomb lungs was 33.3% compared to 7.4% without honeycombing (P=0.004). Multivariate analysis showed that honeycombing was a significant risk factor for tumor size underestimation. A Bland-Altman plot represented wide 95% limits of agreement, -40.8 to 70.2 mm, between the pathological and radiological maximum tumor sizes in honeycomb lungs.

Treatment outcomes of patients with stage III non-small cell lung cancer and interstitial lung diseases receiving intensity-modulated radiation therapy: A single-center experience of 85 cases.

OBJECTIVES: Whether curative-intent radiotherapy could be safely applied to lung cancer patients with interstitial lung diseases (ILD) remains unclear. We aim to evaluate radiation induced lung toxicities (RILTs) and the efficacy of intensity-modulated radiotherapy (IMRT) in these patients. ILD is characterized by inflammation or fibrosis in the interstitial tissue of the lung. MATERIALS AND METHODS: Stage III non-small cell lung cancer (NSCLC) and ILD patients treated with curative-intent IMRT between 2010 and 2019 were retrospectively reviewed. Pre-radiation computed tomography (CT) was scored according to a thin-section CT scoring system for idiopathic pulmonary fibrosis. RESULTS: A total of 85 of 1261 stage III NSCLC patients were found with ILD. Seventeen (20%) of them developed G3+ (greater than or equal to grade 3) RILTs. The incidence abruptly dropped to 11.1%, 3.8%, and 0% for patients with honeycombing score ≤1, V20 <20%, or both, respectively. Multivariate analysis showed that honeycombing score >1 and V20 ≥20% were independently associated with higher risk of G3+ RILTs. The median overall survival (OS) and progression-free survival (PFS) were 14.0 months and 7.4 months in the whole group, whereas 26.5 months and 10.6 months in the low-risk group (patients with honeycombing score <1 and V20 <20%). In the univariate analysis for overall survival, G3+ RILTs were evaluated as risk factors (p = 0.026) and low-risk group as the only protective factor (p = 0.063). In the multivariate analysis, G3+ RILTs were the only independent risk factor for OS. CONCLUSION: Honeycombing score >1 and V20 ≥20% were associated with high incidence of RILTs. However, patients with low risk might benefit from IMRT with acceptable toxicities and durable OS.