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High-resolution computed tomography (HRCT) imaging is critical for diagnostic evaluation of Idiopathic Pulmonary Fibrosis (IPF). However, several other interstitial lung diseases (ILDs) often exhibit radiologic pattern similar to IPF on HRCTmaking the diagnosis of the disease difficult. Therefore, biomarkers that distinguish IPF from other ILDs can be a valuable aid in diagnosis. Usingmass spectrometry, we performed proteomic analysis of plasma extracellular vesicles (EVs) in patients diagnosed with IPF, chronic hypersensitivity pneumonitis, nonspecific interstitial pneumonitis, and healthy subjects. A five-protein signature was identified by lasso regression and was validated in an independent cohort using ELISA. The five-protein signature derived from mass spectrometry data showed an area under the receiver operating characteristic curve of 0.915 (95%CI: 0.819-1.011) and 0.958 (95%CI: 0.882-1.034) for differentiating IPF from other ILDs and from healthy subjects, respectively. Stepwise backwards elimination yielded a model with 3 and 2 proteins for discriminating IPF fromother ILDs and healthy subjects, respectively, without compromising diagnostic accuracy. In summary, we discovered and validated EV protein biomarkers for differential diagnosis of IPF in independent cohorts. Interestingly, the biomarker panel could also distinguish IPF and healthy subjects with high accuracy. The biomarkers need to be evaluated in large prospective cohorts to establish their clinical utility. [ABSTRACT FROM AUTHOR]

Systemic sclerosis (SSc) is one of the chronic autoimmune diseases characterized by the infiltration of excess collagen in various organs, especially the skin. It is found to be associated with a higher prevalence of internal malignancies, particularly lung carcinoma. Herein, we report a case of adenosquamous carcinoma confining within the lung in a patient who had long-standing SSc. She was a 55-year-old female patient presenting with progressive dry cough and breathlessness for six months. She had been a known case of diffuse cutaneous SSc for over a decade, based on 2013 American College of Rheumatology (ACR) criteria. The diagnosis is made based on her findings of bilateral thickening of the fingers on both hands, extending up to the metacarpophalangeal joints. Furthermore, she had telangiectasia at the upper chest wall and neck, multiple pitting scars at the toes, Raynaud's esophageal dilatation, and interstitial lung disease (ILD). She had been treated on Mycophenolate Mofetil 500 mg twice daily and low-dose prednisolone 5 mg once daily for 10 years. The patient's high-resolution computed tomography (HRCT) of the chest revealed a subpleural nodule in the posterior basal segment of the left lower lobe with areas of reticular opacities and interlobular septal thickening on bilateral lung fields six months earlier. The current computed tomography of the lung revealed a new 2.6 x 2.5 cm ill-defined lesion with irregular margins at the left lower lobe. A CT-guided biopsy was done for the lesion, which revealed adenosquamous carcinoma. Immunohistochemistry was consistent with a diagnosis of primary pulmonary adenosquamous carcinoma. The patient did not accept any further investigations and/or treatment. Herein, we present a rare lung malignancy, adenosquamous carcinoma of the lung with an underlying long-term diffuse cutaneous SSc in a nonsmoking female, which highlights the importance of lung cancer screening in individuals with SSc complicated with ILD and supports the fact that there is an increased prevalence of lung cancer among SSc-ILD patients than that of the regular population., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, C et al.)

Idiopathic pulmonary fibrosis (IPF) is the most common of the idiopathic interstitial pneumonias. Its signs and symptoms are relatively non-specific, and patients often present with chronic cough, progressive dyspnea, resting or exertional hypoxemia, and inspiratory crackles on lung auscultation. Definitive diagnosis requires the exclusion of known causes of pulmonary fibrosis and identification of the usual interstitial pneumonia (UIP) pattern of disease either on high-resolution computed tomography (HRCT) scan of the chest or on surgical lung biopsy. Multidisciplinary discussion involving pulmonologists, radiologists, and pathologists with expertise in the diagnosis of IPF and other forms of interstitial lung disease is recommended and often required. Management focuses on anti-fibrotic therapy and early referral to lung transplant centers for those who are candidates. This review will discuss the current recommendations for the diagnosis, prognostication, and management of patients with IPF. [ABSTRACT FROM AUTHOR]

Abstract This study aimed to determine whether a surgical lung biopsy is essential for IPF diagnosis with the possible UIP CT pattern. We performed literature searches of the MEDLINE and EMBASE databases and included studies that conducted a radiologic-pathologic evaluation of IPF according to the 2011 guideline. Outcomes were pooled using a random-effects model. Twelve studies were included. Pooled proportions of IPF for a UIP pattern were 99% (95%CI, 93% to 100%; I2 = 51.7%) and for a possible UIP pattern were 94% (scenario inclusive of probable IPF; 95%CI, 87% to 99%; I2 = 82.9%) and 88% (scenario exclusive of probable IPF; 95%CI, 79% to 95%; I2 = 82.7%). The pooled percentage difference in the proportion of IPF between the UIP and possible UIP patterns was −2% (95%CI, −4% to 1%; I2 = 0.0%) in the former scenario and 4% (95%CI, 0% to 8%; I2 = 0.1%) in the latter scenario. The proportion of IPF with the possible UIP pattern was moderately correlated with the prevalence of IPF (correlation coefficient, 0.605; 95%CI, 0.550–0.860). There was a negligible pooled percentage difference in the proportion of IPF between the UIP and possible UIP patterns, indicating that IPF diagnosis can be confirmed without biopsy in suspected IPF cases with the possible UIP pattern.

A diagnostic work-up for Idiopathic Pulmonary Fibrosis (IPF) requires the exclusion of other nosological entities with a radiological and histopathological pattern of Usual Interstitial Pneumonia (UIP). A UIP pattern associated with positive Anti-Neutrophil Cytoplasmatic Antibodies (ANCA) testing, particularly with anti-Myeloperoxidase (MPO) positivity, which may develop into microscopic polyangiitis, is a nosological entity which was described over a decade ago by several authors; however, its systematic serological exclusion in IPF diagnosis is not recommended by the world's leading scientific societies. This article presents the case of a patient with a radiological "UIP probable" and histopathological "UIP definite" pattern who was initially diagnosed with IPF and was therefore treated with antifibrotic therapy; however, by the fourth year of clinical follow-up the patient developed MPO-positive microscopic polyangiitis with severe progressive renal failure. [ABSTRACT FROM AUTHOR]

Purpose: Radiologic diagnosis of chronic hypersensitivity pneumonitis (CHP) presenting a usual interstitial pneumonia (UIP) pattern is challenging. The aim of this study was to identify the high-resolution CT (HRCT) findings which are useful to discriminate CHP-UIP from idiopathic pulmonary fibrosis (IPF).Materials and Methods: This study included 49 patients with well-established bird-related CHP-UIP, histologically confirmed, and 49 patients with IPF. Two groups of observers independently assessed HRCT, evaluated the extent of each abnormal HRCT finding. When their radiological diagnosis was CHP-UIP, they noted the HRCT findings inconsistent with IPF.Results: Correct CT diagnoses were made in 79% of CHP-UIP and 53% of IPF. Although no apparent difference was seen in the extent of each HRCT finding, upper or mid-lung predominance, extensive ground-glass abnormality, and profuse micronodules were more frequently pointed out as inconsistent findings in CHP-UIP than IPF (p = 0.007, 0.010, 0.001, respectively). On regression analysis, profuse micronodules [OR 13.34 (2.85-62.37); p = 0.001] and upper or mid-lung predominance of findings [OR 2.86 (1.16-7.01); p = 0.022] remained as variables in the equation.Conclusion: In this cohort, some IPF cases were misdiagnosed as CHP-UIP. Profuse micronodules and upper or mid-lung predominance are important clues for the differentiation of CHP-UIP from IPF. [ABSTRACT FROM AUTHOR]

The diagnosis and classification of systemic sclerosis-associated interstitial lung disease (SSc-ILD) is essential to improve the prognosis of systemic sclerosis (SSc) patients. The risk-stratification of disease severity and follow-up requires a multidisciplinary approach, integrating high-resolution computed tomography (HRTC) of the lung, pulmonary function tests (PFT), along with clinical and symptomatic evaluations. The use of HRCT in detecting SSc-ILD is not so much based on a definitive validation, but rather reflects the widespread clinician recognition of dissatisfaction with other modalities. However, due to the heterogeneity of SSc-ILD and the potential absence of symptoms in early or mild disease, it is prudent to consider as many parameters as possible in the assessment and monitoring of newly diagnosed patients. An early diagnosis meets the primary goal, i.e., the prevention of disease progression. The current first line treatment regimens are mainly centered on immunosuppressive therapy. This review assesses the role HRCT plays in optimizing care and improving clinical outcomes in SSc-ILD patients.

Background and objectives: The aims of the study were to evaluate the utility of neutrophil-to-lymphocyte ratio (NLR) and the systemic immune-inflammation index (SII) as inflammation markers and prognostic factors in patients with known interstitial lung disease secondary to connective tissue diseases (CTD-ILD) compared with idiopathic pulmonary fibrosis (IPF). Materials and Methods: Forty-two patients with known interstitial lung disease (21 with IPF and 21 with CTD-ILD) and 42 control matched healthy patients were included. The NLR was calculated as the absolute neutrophil count divided by the absolute lymphocyte count, and the SII was calculated as follows: SII = platelets × neutrophils/lymphocytes, with the data being obtained from the patients data charts at admission, before any treatment. Results: our hypothesis was that in patients with interstitial lung disease NLR and SII would have higher values compared with patients with CTD-ILD or control healthy patients. The mean NLR value was 3.01 (±1.35) among patients with idiopathic pulmonary fibrosis, and 2.38 (±1.08) among patients with CTD-ILD without significant statistical difference (p = 0.92). There was however a clinically significant statistical difference when compared with the control group, where NLR was 2.00 (±1.05) (p = 0.003). SII values were 619.37 (±329.51) in patients with IPF, 671.55 (±365.73) in CTD-ILD group and 569.73 (±326.67) in healthy subjects (p = 0.13) Conclusions: A mean NLR value of 2.8 and a SII value over 500 in patients with connective diseases can become a marker of pulmonary interstitial involvement. In the context of non-exacerbated interstitial lung disease, NLR and SII have reduced numerical values, without being statistically correlated with prognosis when we compared with patients with connective tissue diseases without exacerbation or with healthy people, the cut off being of 2.4. However subsequent studies in larger patient samples might provide changes in these cut-off values.

Abstract A 64-year-old man was admitted to our hospital with an abnormal chest shadow. The patient was a current-smoker and had a past illness of autoimmune pancreatitis with a high serum level of IgG4, 348 mg/dL. Chest CT showed upper-lobe emphysema, and lower-lobe reticulation with honeycombing, suggestive of combined pulmonary fibrosis with emphysema (CPFE). Surgical lung biopsy was revealed a usual interstitial pneumonia pattern with marked infiltration of IgG4-positive plasma cells. The patient was diagnosed with IgG4 related disease (IgG4-RD) presenting with CPFE. Pulmonary manifestation was improved by corticosteroid therapy. IgG4-RD may be an underlying condition in patient with CPFE. [ABSTRACT FROM AUTHOR]

Purpose of Review: Among the many extra-articular complications of rheumatoid arthritis (RA), interstitial lung disease (ILD) contributes significantly to morbidity and mortality. Prevalence estimates for RA-ILD vary widely depending on the specific clinical, radiographic, and functional criteria used to establish the diagnosis. A key unresolved issue is whether early, subclinical forms of RA-ILD represent a precursor to end stage, fibrotic lung disease. Based on uncertainties surrounding the natural history of RA-ILD, incomplete understanding of underlying disease pathogenesis, and lack of controlled clinical trials, evidence-based therapeutic strategies remain largely undefined. Recent Findings: Correlative clinico-epidemiological studies have identified key risk factors for disease progression. Complementing these findings, the identification of specific molecular and serological markers of RA-ILD has improved our understanding of disease pathogenesis and established the foundation for predictive biomarker profiling. Experience from case series and cohort studies suggests that newer biological agents such as rituximab may be viable treatment options. Summary: RA-ILD continues to have a major impact on 'disease intrinsic' morbidity and mortality. Increased understanding of disease pathogenesis and the natural history of subclinical RA-ILD will promote the development of more refined therapeutic strategies. [ABSTRACT FROM AUTHOR]

Objective. To compare the survival outcomes between myositis-associated usual interstitial pneumonia (MA-UIP) and idiopathic pulmonary fibrosis (IPF-UIP). Methods. Adult MA-UIP and IPF-UIP patients were identified using CTD and IPF registries. The MA-UIP cohort included myositis or anti-synthetase syndrome patients with interstitial lung disease while manifesting UIP on high-resolution CT chest and/or a lung biopsy revealing UIP histology. IPF subjects met American Thoracic Society criteria and similarly had UIP histopathology. Kaplan_Meier survival curves compared cumulative and pulmonary event-free survival (event = transplant or death) between (i) all MAUIP and IPF-UIP subjects, (ii) MA-UIP with biopsy proven UIP (n = 25) vs IPF-UIP subjects matched for age, gender and baseline forced vital capacity (±10%). Cox proportional hazards ratios compared the survival controlling for co-variates. Results. Eighty-one IPF-UIP and 43 MA-UIP subjects were identified. The median cumulative and eventfree survival time in IPF vs MA-UIP was 5.25/1.8 years vs 16.2/10.8 years, respectively. Cumulative and event-free survival was significantly worse in IPF-UIP vs MA-UIP [hazards ratio of IPF-UIP was 2.9 (95% CI: 1.5, 5.6) and 5.0 (95% CI: 2.8, 8.7) (P<0.001), respectively]. IPF-UIP event-free survival (but not cumulative) remained significantly worse than MA-UIP with a hazards ratio of 6.4 (95% CI: 3.0, 13.8) after controlling for age at interstitial lung disease diagnosis, gender, ethnicity and baseline forced vital capacity%. Respiratory failure was the most common cause of death in both groups. A sub-analysis of 25 biopsy-proven MA-UIP subjects showed similar results. Conclusion. MA-UIP patients demonstrated a significant survival advantage over a matched IPF cohort, suggesting that despite similar histological and radiographic findings at presentation, the prognosis of MAUIP is superior to that of IPF-UIP. [ABSTRACT FROM AUTHOR]

Purpose: The objective of the study was to determine whether HRCT criteria for Usual Interstitial Pneumonia (UIP), possible UIP or no-UIP pattern recommended by ATS/ERS/JRS/ALAT guidelines 2011 are able to predict progression and prognosis of the disease in a group of patients with fibrotic idiopathic interstitial pneumonia (IIP). Materials and methods: This was a retrospective study conducted with the approval of the ethics committee. Two radiologists at baseline HRCT distributed 70 patients with fibrotic IIP into three groups on the basis of the 2011 guidelines: UIP pattern (group 1), possible UIP pattern (group 2), inconsistent with UIP pattern (group 3). The different abnormalities (honeycombing, reticulation, ground-glass and traction bronchiectasis), fibrotic score (reticulation + honeycombing) and overall CT score were visually scored at baseline and during the follow-up (total HRCT 178). The mortality rate of the three groups was compared. The baseline abnormalities were then correlated with the mortality rate in the UIP group. Results: The inter-observer agreement in the classification of the abnormalities in the three groups was almost perfect ( k = 0.92). After consensus, 44 patients were classified into group 1, 13 into group 2 and 13 into group 3. During a mean follow-up of 1386 days, overall CT score, fibrotic score, honeycombing and traction bronchiectasis showed a significant progression in group 1. The mortality rate was significantly higher in group 1 (18 deaths) versus group 2 and 3 (1 death each). In group 1, baseline honeycombing rate higher than 25 %, fibrotic score higher than 30, overall CT score greater than 45 and traction bronchiectasis in more than 4 lobes defined the worst prognosis. Conclusion: HRCT classification based on 2011 guidelines showed high accuracy in stratifying fibrotic changes because in our study UIP, possible UIP and inconsistent with UIP pattern seem to be correlated with different disease progression and mortality rate. [ABSTRACT FROM AUTHOR]

Background: Due to the small amount of alveolar tissue in transbronchial biopsy (TBB) by forceps, the diagnosis of diffuse, parenchymal lung diseases (DPLD) is inherently problematic, with an overall low yield. The use of cryotechnique in bronchoscopy, including TBB by cryoprobe, has revealed new opportunities in the endoscopical diagnosis of malignant and non-malignant lung diseases. Methods: To evaluate TBB by cryotechnique for non-neoplastic lung diseases, we analyzed 52 patients (mean age 63 ± 13 years) with unclear DPLD. These individuals underwent bronchoscopy with TBB by cryoprobe. Thereafter histopathological results were compared with the clinically evaluated diagnosis. Results: No major complications were seen. Mean specimen diameter in the histological biopsies was 6.9 ± 4.4 mm (Range 2 - 22 mm). A correlation between clinical and histopathological diagnoses was found in 79% of cases (41/52). In the case of UIP (usual interstitial pneumonia) pattern, the concordance was 10/15 (66%). Conclusion: Based on these results TBB by cryotechnique would appear to be a safe and useful method that reveals new perspectives for the endoscopical diagnosis of DPLD. [ABSTRACT FROM AUTHOR]

Abstract: The aim of the study is to delineate the relation between cigarette smoking and the development of interstitial lung disease with declaration of the different types of the interstitial lung associated with smoking. HRCT was done on 40 smokers. All patients had thorough clinical assessment. Blood gases were estimated in all patients. Pulmonary function tests were done to all subjects, BAL was done in 27 patients, and trans-bronchial biopsy was done in 14 patients. None of the patients agreed to do any surgical biopsies. In 25 patients (n =25, 62.5%) the HRCT findings suggested RB-ILD. Five patients (n =5, 12.5%), were diagnosed as early DIP. Three patients (n =3, 7.5%) showed advanced DIP. In six patients (n =6, 15%) the findings suggests UIP and one patient (30year-old) had findings suggesting PLCH. In the appropriate clinical context high-resolution CT plays an integral role in the evaluation of SR-ILD, the presence of typical changes at high-resolution CT renders the diagnosis almost certain and may obviate further testing. Lung biopsy may be needed when the findings at high-resolution CT are relatively nonspecific or when a confident definitive diagnosis is needed. [Copyright &y& Elsevier]

A 69-year-old man was diagnosed with immunoglobulin (Ig) G4-related disease (IgG4-RD) at 62 years old. At that time, he had high serum IgG4 levels and bilateral submandibular gland swelling on CT; thus, a gland biopsy was performed. Because a reticular shadow was found on chest CT, a lung surgical biopsy was also performed. The specimens revealed usual interstitial pneumonia (UIP) pattern interstitial pneumonia with some IgG4-positive cells. The patient was subsequently followed up without treatment. His forced vital capacity and radiological findings progressively deteriorated, consistent with UIP pattern interstitial lung disease but different from a lung lesion of IgG4-RD.

Abstract: Adenosine (ADO) is a retaliatory metabolite that is expressed in conditions of injury or stress. During these conditions ATP is released at the extracellular level and is metabolized to adenosine. For this reason, adenosine is defined as a “danger signal” for cells and organs, in addition to its important role as homeostatic regulator. Its physiological functions are mediated through interaction with four specific transmembrane receptors called ADORA1, ADORA2A, ADORA2B and ADORA3. In the lungs of mice and humans all four adenosine receptors are expressed with different roles, having pro- and anti-inflammatory roles, determining bronchoconstriction and regulating lung inflammation and airway remodeling. Adenosine receptors can also promote differentiation of lung fibroblasts into myofibroblasts, typical of the fibrotic event. This last function suggests a potential involvement of adenosine in the fibrotic lung disease processes, which are characterized by different degrees of inflammation and fibrosis. Idiopathic pulmonary fibrosis (IPF) is the pathology with the highest degree of fibrosis and is of unknown etiology and burdened by lack of effective treatments in humans. [Copyright &y& Elsevier]

Different anatomic and physiological changes occur in the lung of aging people that can affect pulmonary functions, and different pulmonary diseases, including deadly diseases such as chronic obstructive pulmonary disease (COPD)/emphysema and idiopathic pulmonary fibrosis (IPF), can be related to an acceleration of the aging process. The individual genetic background, as well as exposure to a variety of toxic substances (cigarette smoke in primis) can contribute significantly to accelerating pulmonary senescence. Premature aging can impair lung function by different ways: by interfering specifically with tissue repair mechanisms after damage, thus perturbing the correct crosstalk between mesenchymal and epithelial components; by inducing systemic and/or local alteration of the immune system, thus impairing the complex mechanisms of lung defense against infections; and by stimulating a local and/or systemic inflammatory condition (inflammaging). According to recently proposed pathogenic models in COPD and IPF, premature cellular senescence likely affects distinct progenitors cells (mesenchymal stem cells in COPD, alveolar epithelial precursors in IPF), leading to stem cell exhaustion. In this review, the large amount of data supporting this pathogenic view are discussed, with emphasis on the possible molecular and cellular mechanisms leading to the severe parenchymal remodeling that characterizes, in different ways, these deadly diseases. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) is the most common systemic autoimmune disease in the United States, affecting 1% to 2% of the adult population. Although joints and synovium are the primary targets in this disorder, extra-articular manifestations involving the lungs can lead to significant morbidity and excess mortality. Among the various pulmonary complications that occur in RA, interstitial lung disease (ILD) is the most damaging, with effects ranging from subclinical inflammation/scarring to end-stage pulmonary fibrosis. New insights during the past several years have underscored the epidemiologic impact of clinically/functionally significant RA-associated ILD (RA-ILD) and have begun to identify factors contributing to the pathogenesis of this potentially devastating complication of RA. Despite these advancements, the complexity of RA-ILD and the lack of reliable predictors for disease progression highlight the need for improved biomarker development. Establishing such detailed molecular signatures will ultimately guide the application and timing of therapeutic agents that include immunomodulators as well as newly studied antifibrotic agents. [ABSTRACT FROM AUTHOR]

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Objective: A retrospective study was carried out in two institutions to determine serial changes in the pattern, distribution, and extent of interstitial lung disease (ILD) associated with polymyositis (PM)–dermatomyositis (DM) using HRCT. Subjects and methods: Twenty patients with PM–DM and clinical suspicion of ILD who underwent at least two serial HRCT examinations were retrospectively evaluated by two readers. Patients were classified according to the dominant CT pattern which was correlated with clinical evolution and underlying histology when available (n=6). Results: Patients were classified into four groups according to the dominant pattern: ground-glass attenuation and reticulation (group 1, n=9); honeycombing (group 2, n=4); airspace consolidation (group 3, n=4), and normal or almost normal lung (group 4, n=3). Under medical treatment, serial HRCT showed that the extent of areas of ground-glass opacities (group 1) decreased in five patients, stabilized in two, and increased in two. Pathologic findings demonstrated usual interstitial pneumonia (UIP) in two cases and unspecified interstitial pneumonia in one. In group 2, extent of honeycombing increased in three cases and stabilized in one. In group 3, dramatic resolution of airspace consolidation occurred in three cases. Clinical deterioration with extensive consolidation at CT and diffuse alveolar damage (DAD) at histology occurred in one patient of each of the three previous groups. Lesions stayed invisible or progressed slightly in the fourth group. Conclusion: In ILD associated with PM–DM, clinical deterioration and DAD in the follow-up can be observed whatever the HRCT pattern. However, unfavorable evolution is constant when honeycombing is present at the initial CT. [Copyright &y& Elsevier]

The diagnosis and classification of systemic sclerosis-associated interstitial lung disease (SSc-ILD) is essential to improve the prognosis of systemic sclerosis (SSc) patients. The risk-stratification of disease severity and follow-up requires a multidisciplinary approach, integrating high-resolution computed tomography (HRTC) of the lung, pulmonary function tests (PFT), along with clinical and symptomatic evaluations. The use of HRCT in detecting SSc-ILD is not so much based on a definitive validation, but rather reflects the widespread clinician recognition of dissatisfaction with other modalities. However, due to the heterogeneity of SSc-ILD and the potential absence of symptoms in early or mild disease, it is prudent to consider as many parameters as possible in the assessment and monitoring of newly diagnosed patients. An early diagnosis meets the primary goal, i.e., the prevention of disease progression. The current first line treatment regimens are mainly centered on immunosuppressive therapy. This review assesses the role HRCT plays in optimizing care and improving clinical outcomes in SSc-ILD patients. [ABSTRACT FROM AUTHOR]

Following the introduction of a novel pathological concept of usual interstitial pneumonia (UIP) by Liebow and Carrington in 1969, diffuse interstitial pneumonia has evolved into UIP, nonspecific interstitial pneumonia (NSIP), and interstitial lung abnormality (ILA); the histopathological and CT findings of these conditions reflect the required multidisciplinary team approach, involving pulmonologists, radiologists, and pathologists, for their diagnosis and management. Concomitantly, traction bronchiectasis and bronchiolectasis have been recognized as the most persistent and important indices of the severity and prognosis of fibrotic lung diseases. The traction bronchiectasis index (TBI) can stratify the prognoses of patients with ILAs. In this review, the evolutionary concepts of UIP, NSIP, and ILAs are summarized in tables and figures, with a demonstration of the correlation between CT findings and pathologic evaluation. The CT-based UIP score is being proposed to facilitate a better understanding of the spectrum of pulmonary fibrosis, from ILAs to UIP, with emphasis on traction bronchiectasis/bronchiolectasis., Competing Interests: Dr. Hatabu reports grants from Canon Medical Systems Inc, grants from Konica Minolta Inc, personal fees from Mitsubishi Chemical Co, personal fees from Canon Medical Systems Inc, outside the submitted work. Other authors have no potential conflicts of interest to disclose., (Copyright © 2021 The Korean Society of Radiology.)

Introduction: High-Resolution Computed Tomography (HRCT) plays a pivotal role in the diagnosis of Idiopathic Pulmonary Fibrosis (IPF). First, it establishes the presence of lung fibrosis. Second, it allows the recognition of specific patterns, namely typical and probable Usual Interstitial Pneumonia (UIP) pattern obviating the need for tissue confirmation in the appropriate clinical context., Areas Covered: Acknowledging the extreme versatility of modern radiology and the heavy burden of knowledge the modern radiologist has to cope with, this review addresses the diagnostic pitfalls of honeycombing in IPF diagnosis. This review focuses on two areas: i) when honeycombing is actually present but there are other findings that should raise suspicion of an alternative diagnosis and ii) when honeycombing is misdiagnosed, focusing on the commonest radiographic patterns that are responsible for this confusion., Expert Opinion: It is pivotal to establish the actual presence of honeycombing. Even then, the distribution of honeycombing or the presence of other findings could be suggestive of alternative diagnoses. Reviewing older images can be extremely helpful in reaching the correct diagnosis.

Background and objectives: The aims of the study were to evaluate the utility of neutrophil-to-lymphocyte ratio (NLR) and the systemic immune-inflammation index (SII) as inflammation markers and prognostic factors in patients with known interstitial lung disease secondary to connective tissue diseases (CTD-ILD) compared with idiopathic pulmonary fibrosis (IPF). Materials and Methods: Forty-two patients with known interstitial lung disease (21 with IPF and 21 with CTD-ILD) and 42 control matched healthy patients were included. The NLR was calculated as the absolute neutrophil count divided by the absolute lymphocyte count, and the SII was calculated as follows: SII = platelets × neutrophils/lymphocytes, with the data being obtained from the patients data charts at admission, before any treatment. Results: our hypothesis was that in patients with interstitial lung disease NLR and SII would have higher values compared with patients with CTD-ILD or control healthy patients. The mean NLR value was 3.01 (±1.35) among patients with idiopathic pulmonary fibrosis, and 2.38 (±1.08) among patients with CTD-ILD without significant statistical difference ( p = 0.92). There was however a clinically significant statistical difference when compared with the control group, where NLR was 2.00 (±1.05) ( p = 0.003). SII values were 619.37 (±329.51) in patients with IPF, 671.55 (±365.73) in CTD-ILD group and 569.73 (±326.67) in healthy subjects ( p = 0.13) Conclusions: A mean NLR value of 2.8 and a SII value over 500 in patients with connective diseases can become a marker of pulmonary interstitial involvement. In the context of non-exacerbated interstitial lung disease, NLR and SII have reduced numerical values, without being statistically correlated with prognosis when we compared with patients with connective tissue diseases without exacerbation or with healthy people, the cut off being of 2.4. However subsequent studies in larger patient samples might provide changes in these cut-off values.

Background: Reactive oxygen species (ROS) can play a role in the pathogenesis of Idiopathic Pulmonary Fibrosis (IPF) by contributing to epithelial damage. Bcl-2-like 11 ( BIM ) is involved in the generation of ROS via forkhead box O3 (FOXO3), and a BIM deletion polymorphism related to apoptosis has been reported to be specific to Asians. Here we examine the clinical features of IPF in patients with BIM deletion polymorphism., Methods: In this single-center retrospective study, we reviewed the medical records of 63 patients with IPF who were treated at our hospital from January 2006 through April 2018. Patients with and without BIM deletion polymorphism were compared in relation to clinical characteristics, pulmonary function test results, frequency of acute exacerbation (AE)-IPF, and redox status [including oxidized glutathione (GSSG), reduced glutathione (GSH), 8-hydroxy-2'-deoxyguanosine (8-OHdG), and 8-isoprostane (8-iso)] at baseline and at 1 and 2 years after treatment., Results: No fatal AE-IPF occurred in patients with BIM deletion polymorphism (0% vs. 36.4% of polymorphism-negative cases; P=0.038). Change in forced vital capacity from baseline (ΔFVC) at 2 years was significantly lower in patients with the BIM deletion polymorphism than in those without the polymorphism (‒0.42±0.50 vs. ‒0.88±0.83 L, respectively; P=0.045). Total blood glutathione (tGSH) was significantly higher in patients with the deletion polymorphism than in those without the polymorphism (988±48.3 vs. 858±25.8 µM, respectively; P=0.042). 8-iso was significantly lower in the former group (246.1±81.6 vs. 400.9±334.1 pg/mL, respectively; P=0.022)., Conclusions: IPF patients with BIM deletion polymorphism had a good redox balance and may thus have a better clinical outcome than patients without this polymorphism., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.

Background: 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)., Methods: 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., Results: 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)., Conclusions: These results suggest that NSIP and bronchiolitis HRCT patterns may be risk factors for resistance to RA therapy., (Copyright © 2019 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.)

Interstitial Lung Disease (ILD) is a well-known complication of rheumatoid arthritis (RA) which often results in significant morbidity and mortality. It is often diagnosed late in the disease process via descriptive criteria. Multiple subtypes of RA-ILD exist as defined by chest CT and histopathology. In the absence of formal natural history studies and definitive diagnostics, a conventional dogma has emerged that there are two major subtypes of RA-ILD (nonspecific interstitial pneumonia (NSIP) and Usual Interstitial Pneumonia (UIP)). These subtypes are based on clinical experience and correlation studies. However, recent animal model data are incongruous with established paradigms of RA-ILD and beg reassessment of the clinical evidence in order to better understand etiology, pathogenesis, prognosis, and response to therapy. To this end, here we: 1) review the literature on epidemiology, radiology, histopathology and clinical outcomes of the various RAILD subtypes, existing animal models, and current theories on RA-ILD pathogenesis; 2) highlight the major gaps in our knowledge; and 3) propose future research to test an emerging theory of RAILD that posits initial rheumatic lung inflammation in the form of NSIP-like pathology transforms mesenchymal cells to derive chimeric disease, and subsequently develops into frank UIP-like fibrosis in some RA patients. Elucidation of the pathogenesis of RA-ILD is critical for the development of effective interventions for RA-ILD., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Atypical idiopathic pulmonary fibrosis (IPF) including multiple cysts or markedly atelectatic induration in upper lung predominance occasionally can confirm the diagnosis of IPF through a multidisciplinary discussion (MDD) between clinician, radiologist and, pathologist in clinical practice. The aim of this study was to clarify the differences in clinico-radiological characteristics and the efficacy of anti-fibrotic agents between atypical IPF and typical IPF., Methods: We retrospectively evaluated the differences in clinico-radiological characteristics between patients with atypical IPF (n=44) and those with typical IPF (n=87) and examined efficacy of anti-fibrotic agents in atypical IPF. Atypical IPF was characterized by the presence of markedly atelectatic induration in upper lung predominance (pleuroparenchymal fibroelastosis; PPFE like lesion) with and without multiple thick-walled large cysts (TWLC), so-called macrocystic honeycombing (TWLC; >2.5 cm in diameter with 1-3 mm thickness) in addition to honeycombing in the bilateral lower lobes predominance., Results: There was no difference in the baseline disease severity for IPF between both groups. The annual change value of fibrotic score and traction bronchiectasis (TBE) score, and decreased changes in forced vital capacity (FVC) during 6 months were significantly higher in atypical IPF than those in typical IPF. Survival time was significantly lower in patients with atypical IPF (MST: 33.4 vs. 47.9 months, P=0.03). The multivariate Cox regression model demonstrated that the prognostic predictors were presence of atypical IPF and increased Gender-Age-Physiology (GAP) staging. Moreover, the rate of decrease in FVC value 6 months after treatment with anti-fibrotic agents was significantly higher in atypical IPF than those in typical IPF (-11.8%±14.0% vs. -1.0%±12.7%; P=0.01)., Conclusions: This study demonstrated that the prognosis for atypical IPF was significantly worse than that for typical IPF. Future studies are required prospective analyses of efficacy of anti-fibrotic agents for patients with atypical IPF., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.

Background: The clinicopathological characteristics of lung cancer with concomitant usual interstitial pneumonia (UIP) are insufficiently understood. This study aimed to elucidate a characteristic pathological feature of lung cancer that develops in patients with UIP, with a focus on the location of its onset., Methods: We reviewed surgically obtained specimens, including 547 tumors from 526 patients who underwent lobectomy for lung cancer. Surveyed patients were classified into three groups: patients with UIP (UIP group), patients with lung pathology other than UIP (non-UIP group), and patients without any associated lung pathology (normal group). The histology as well as the lobe and location of the onset of lung cancer were compared among these groups. The peripheral location was subdivided into subpleural, inner and tumor involved centrally secondary to extension., Results: The UIP group comprised 82 patients (male, 71 [87%]; mean age, 71 years; smoking rate, 94%), the non-UIP group comprised 334 patients (male, 267 [80%]; mean age, 69 years; smoking rate, 81%), and the normal group comprised 110 patients (male, 33 [30%]; mean age, 63; smoking rate, 29%). No statistical differences were noted in sex, mean age, or smoking index between the UIP and non-UIP groups. Compared with the non-UIP group, the frequency of squamous cell carcinoma (63% vs. 32%), lower lobe origin (76% vs. 32%), and subpleural location (24% vs. 5%) were significantly higher in the UIP group., Conclusions: Lung cancers in patients with UIP show a predilection for the subpleural region, where UIP is also thought to originate., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background Idiopathic pulmonary fibrosis (IPF) is a clinical form of usual interstitial pneumonia (UIP). Computed chest tomography (CT) has a fundamental role in the multidisciplinary diagnostics. However, it has not been verified if and how a subjective opinion of a radiologists or pneumologists can influence the assessment and overall diagnostic summary. Purpose To verify the reliability of the scoring system. Material and Methods Assessment of conformity of the radiological score of high-resolution CT (HRCT) of lungs in patients with IPF was performed by a group of radiologists and pneumologists. Personal data were blinded and the assessment was performed independently using the Dutka/Vasakova scoring system (modification of the Gay system). The final score of the single assessors was then evaluated by means of the paired Spearman’s correlation and analysis of the principal components. Results Two principal components explaining cumulatively a 62% or 73% variability of the assessment of the single assessors were extracted during the analysis. The groups did not differ both in terms of specialty and experience with the assessment of the HRCT findings. Conclusion According to our study, scoring of a radiological image using the Dutka/Vasakova system is a reliable method in the hands of experienced radiologists. Significant differences occur during the assessment performed by pneumologists especially during the evaluation of the alveolar changes. [ABSTRACT FROM AUTHOR]

Background: Previous studies have reported conflicting survival rates for connective tissue disease (CTD)-associated usual interstitial pneumonia (UIP) and idiopathic pulmonary fibrosis (IPF/UIP). This study investigated the differences in the clinical characteristics and prognoses of patients diagnosed with CTD-UIP and IPF/UIP., Methods: A retrospective review of patients with IPF (n=88) and CTD-UIP (n=67) from January 2008 to June 2013 was completed. We compared the demographics and clinical characteristics between the two groups. Survival rates were compared using a log-rank and Cox proportional hazard regression analysis., Results: Undifferentiated-CTD (UCTD) accounted for 33% of the established CTD-UIP cases. No significant differences were identified in the demographic characteristics or physiological parameters between the UCTD and CTD patients (all P>0.05). However, the CTD-UIP patients were more likely to be young, female, and nonsmokers compared with the IPF/UIP group (all P<0.01). There was no difference in survival between the IPF/UIP and CTD-UIP patients [hazard ratio (HR), 1.74; 95% confidence interval (CI), 0.86-3.50; P=0.113]. However, the removal of the UCTD patients from the CTD group revealed that IPF/UIP was associated with a 2.47-fold increased risk of mortality compared with CTD-UIP (HR, 2.47; 95% CI, 1.01-6.09; P=0.049)., Conclusions: Our findings indicate that the survival of CTD-UIP patients was similar compared with that of IPF/UIP patients. However, it appears that UCTD influences the survival rate of CTD-UIP patients.

Background: Nonspecific interstitial pneumonia (NSIP) has recently been proposed as a histologic type of idiopathic interstitial pneumonia (IIP), but its broad spectrum of clinicopathologic findings and variable prognosis are poorly understood. It is particularly unclear how NSIP and usual interstitial pneumonia (UIP) are related. The present study investigated the clinicopathologic features and prognosis of NSIP, and its differential diagnosis from UIP., Methods: The clinicopathologic findings and prognosis in 21 NSIP and 18 UIP patients who underwent surgical or video-assisted thoracoscopic lung biopsy were reviewed., Results: NSIP was more frequent in women and showed nonspecific clinical manifestations. High-resolution computed tomography (HRCT) demonstrated ground-glass, net-like, and patchy attenuation in both lungs. Semiquantitative HRCT showed a median fibrosis score of 3 (range, 0 to 7) in NSIP patients and 5 (range, 2 to 7) in UIP patients (P<0.01). On histopathologic examination, NSIP cases were heterogeneous and the findings could be categorized into cellular and fibrosing patterns. The mean age of the NSIP and UIP patients was 48 and 60 years, respectively. The frequencies of fibroblast foci, myogelosis, honeycomb lesions, and pulmonary structural destruction in NSIP and UIP patients were 16.7% and 100% (P<0.001), 22.2% and 85.7% (P<0.05), 16.7% and 92.9% (P<0.001), and 27.8% and 100% (P<0.05), respectively. The responses to glucocorticoid treatment and the prognosis were significantly greater in NSIP than those in UIP., Conclusions: NSIP was difficult to be differentiated from UIP by general clinical manifestations, but HRCT can be helpful for this purpose. Definitive diagnosis depends on the results of surgical lung biopsy.