Search Results (18)

Background/Objectives: Interstitial lung disease (ILD) is frequently complicated by pulmonary hypertension (PH), which is associated with reduced exercise capacity and poor prognosis. Early and accurate non-invasive detection of PH remains a clinical challenge. This study evaluated whether combining quantitative CT analysis of lung fibrosis with cardiac MRI-derived measures of right ventricular (RV) function improves the diagnostic accuracy of PH in patients with ILD. Methods: We retrospectively analyzed 72 ILD patients who underwent chest CT, cardiac MRI, and right heart catheterization (RHC). Lung fibrosis was quantified using a Gaussian Histogram Normalized Correlation (GHNC) software that computed the proportions of diseased lung, ground-glass opacity (GGO), honeycombing, reticulation, consolidation, and emphysema. MRI was used to assess RV end-systolic volume (RVESV), ejection fraction, and RV longitudinal strain. PH was defined as a mean pulmonary arterial pressure (mPAP) ≥ 20 mmHg and pulmonary vascular resistance ≥ 3 Wood units on RHC. Results: Compared to patients without PH, those with PH (n = 21) showed significantly reduced RV strain (−13.4 ± 5.1% vs. −16.4 ± 5.2%, p = 0.026) and elevated RVESV (74.2 ± 18.3 mL vs. 59.5 ± 14.2 mL, p = 0.003). CT-derived indices also differed significantly: diseased lung area (56.4 ± 17.2% vs. 38.4 ± 12.5%, p < 0.001), GGO (11.8 ± 3.6% vs. 8.65 ± 4.3%, p = 0.005), and honeycombing (17.7 ± 4.9% vs. 12.8 ± 6.4%, p = 0.0027) were all more prominent in the PH group. In receiver operating characteristic curve analysis, diseased lung area demonstrated an area under the curve of 0.778 for detecting PH. This increased to 0.847 with the addition of RVESV, and further to 0.854 when RV strain was included. Combined models showed significant improvement in risk reclassification: net reclassification improvement was 0.700 (p = 0.002) with RVESV and 0.684 (p = 0.004) with RV strain; corresponding IDI values were 0.0887 (p = 0.03) and 0.1222 (p = 0.01), respectively. Conclusions: Combining CT-based fibrosis quantification with cardiac MRI-derived RV functional assessment enhances the non-invasive diagnosis of PH in ILD patients. This integrated imaging approach significantly improves diagnostic precision and may facilitate earlier, more targeted interventions in the management of ILD-associated PH. Full article

Background: Idiopathic pulmonary fibrosis (IPF) and emphysema often coexist in patients with lung cancer (LC), forming a syndrome with combined pulmonary fibrosis and emphysema (CPFE). The three share the pathogenic mechanisms of smoking, chronic inflammation, and oxidative stress. The clinical management of CPFE patients is challenging, but its impact on tumor characteristics, acute exacerbation (AE), and prognosis is still controversial. The purpose of this study was to clarify the effect of CPFE on tumor biological behavior, AE risk, and survival outcome in patients with IPF-LC so as to optimize individualized treatment strategies. Methods: This was a retrospective and single-center study. Newly diagnosed LC patients with IPF, COPD, and normal lungs were recruited in the west China hospital. Patients with IPF were further categorized into CPFE-LC and isolated IPF-LC groups based on the presence of emphysema. Clinical and tumor features, lung function parameters, and prognosis were obtained and compared. Results: Patients with IPF and LC were more common in older men and heavy smokers. IPF-associated tumors had a higher proportion of carrying EGFR wild-type, occurring in the lower lobe of the lung and developing adenocarcinoma and squamous cell carcinoma. Among IPF-LC patients, 68.2% (103/151) met CPFE criteria. Pulmonary function tests demonstrated preserved VC% but significantly reduced FEV1/FVC in CPFE versus non-emphysema IPF (76.3% vs. 80.7%, p = 0.004), alongside elevated CPI and impaired DLCO. CPI ≥ 40 (HR = 2.087, 95%CI: 1.715–6.089, p = 0.012), combined with COPD (HR = 2.281, 95%CI: 1.139–4.569, p = 0.040), isolated IPF (HR = 5.703, 95%CI: 2.516–12.925, p < 0.001), and CPFE (HR = 6.275, 95%CI: 3.379–11.652, p < 0.001), were independent prognostic risk factors in LC patients. The incidence of treatment-induced AEs (49.5% vs. 29.2%, p = 0.038) and AE-related mortality (28.0% vs. 11.8%, p = 0.045) were significantly higher in the CPFE group than in the isolated IPF group. Logistic regression analysis showed that CPFE (OR: 3.494, 95%CI: 2.014–6.063, p = 0.001) was independently associated with the risk of AE-related mortality in patients with LC and IPF. Conclusions: Compared to LC patients with solely IPF, the presence of emphysema had no significant impact on overall survival, but CPFE increased the risk of treatment-triggered AE and was associated with AE-related mortality. In patients with LC, CPFE with AEs had a worse prognosis than IPF with AEs. Full article

Chronic obstructive pulmonary disease (COPD) is a chronic, debilitating condition that affects the lungs and airways. It is characterized by persistent bronchitis, a condition exemplified by the inflammation of the bronchial tubes, the hypersecretion of mucus, emphysema, and the destruction of the airway parenchyma. The combination of these conditions leads to persistent tissue damage, pulmonary fibrosis, and ongoing inflammation of the airways. The inflammatory response in COPD is a complex process that is orchestrated by a wide range of immune cells. These include lung epithelial cells, monocytes, macrophages, neutrophils, eosinophils, and T and B lymphocytes, among others. These cells work together to produce a wide range of inflammatory biomarkers that are involved in the pathogenesis of COPD. Some of the key inflammatory biomarkers that have been identified in COPD include a variety of cytokines, the C-reactive protein/serum albumin ratio, fibrinogen, soluble receptor for advanced glycation endproducts, club/clara cells in the lungs with a molecular weight of 16 kDa, surfactant protein D, adiponectin, reactive oxygen species, and proteases. This review aims to provide a comprehensive overview of the role of immune cells and key inflammatory biomarkers in the development and progression of COPD. It will delve into the intricacies of the inflammatory response in COPD, exploring the various cell types and biomarkers that are involved in this process. By understanding the underlying mechanisms that drive COPD, we can better develop targeted treatments that can help to alleviate the symptoms of COPD. Full article

Combined pulmonary fibrosis and emphysema (CPFE) is a distinct syndrome associated with heavy smoking. The fibrotic component of the disease is generally believed to be superimposed on previously existing pulmonary emphysema, but the mechanisms responsible for these changes remain poorly understood. To better understand the pathogenesis of CPFE, we performed a series of experiments that focused on the relationships between lung elastic fibers, cigarette smoke, and secondary lung injury. The results indicate that even brief smoke exposure predisposes the lung to additional forms of lung injury that may cause alveolar wall fibrosis. The proinflammatory activity of smoke-induced structural alterations in elastic fibers may contribute to this process by enhancing secondary lung inflammation, including acute exacerbations of chronic obstructive pulmonary disease. Furthermore, the levels of the unique elastin crosslinks, desmosine and isodesmosine, in blood, urine, and sputum may serve as biomarkers for the transition from pulmonary emphysema to interstitial fibrosis. While the long-term effects of these inflammatory reactions were not examined, the current studies provide insight into the potential relationships between elastic fiber injury, cigarette smoke, and secondary lung injury. Determining the mechanisms involved in combined pulmonary emphysema and fibrosis and developing a sensitive biomarker for this type of lung injury may permit timely therapeutic intervention that could mitigate the high risk of respiratory failure associated with this condition. Full article

Combined pulmonary fibrosis and emphysema (CPFE) is a clinical syndrome characterized by upper lobe emphysema and lower lobe fibrosis manifested by exercise hypoxemia, normal lung volumes, and severe reduction of diffusion capacity of carbon monoxide. It has varying prevalence worldwide with a male predominance, and with smoking history of more than 40 pack-years being a common risk factor. The unique imaging features of CPFE emphasize its distinct entity, aiding in the timely detection of pulmonary hypertension and lung cancer, both of which are common complications. High-resolution computed tomography (HRCT) is an important diagnostic and prognostic tool, while lung cancer is an independent factor that alters the prognosis in CPFE patients. Treatment options for CPFE are limited, but smoking cessation, usual treatments of pulmonary fibrosis and emphysema, and avoidance of environmental exposures are encouraged. Full article

Pulmonary hypertension (PH) is a pathophysiological disorder, defined by a mean pulmonary arterial pressure (mPAP) > 20 mmHg at rest, as assessed by right heart catheterization (RHC). PH is not a specific disease, as it may be observed in multiple clinical conditions and may complicate a variety of thoracic diseases. Conditions associated with the risk of developing PH are categorized into five different groups, according to similar clinical presentations, pathological findings, hemodynamic characteristics, and treatment strategy. Most chronic lung diseases that may be complicated by PH belong to group 3 (interstitial lung diseases, chronic obstructive pulmonary disease, combined pulmonary fibrosis, and emphysema) and are associated with the lowest overall survival among all groups. However, some of the chronic pulmonary diseases may develop PH with unclear/multifactorial mechanisms and are included in group 5 PH (sarcoidosis, pulmonary Langerhans’ cell histiocytosis, and neurofibromatosis type 1). This paper focuses on PH associated with chronic lung diseases, in which radiological imaging—particularly computed tomography (CT)—plays a crucial role in diagnosis and classification. Radiologists should become familiar with the hemodynamical, physiological, and radiological aspects of PH and chronic lung diseases in patients at risk of developing PH, whose prognosis and treatment depend on the underlying disease. Full article

Combined pulmonary fibrosis and emphysema (CPFE) is a recently recognized syndrome that, as its name indicates, involves the existence of both interstitial lung fibrosis and emphysema in one individual, and is often accompanied by pulmonary hypertension. This debilitating, progressive condition is most often encountered in males with an extensive smoking history, and is presented by dyspnea, preserved lung volumes, and contrastingly impaired gas exchange capacity. The diagnosis of the disease is based on computed tomography imaging, demonstrating the coexistence of emphysema and interstitial fibrosis in the lungs, which might be of various types and extents, in different areas of the lung and several relative positions to each other. CPFE bears high mortality and to date, specific and efficient treatment options do not exist. In this review, we will summarize current knowledge about the clinical attributes and manifestations of CPFE. Moreover, we will focus on pathophysiological and pathohistological lung phenomena and suspected etiological factors of this disease. Finally, since there is a paucity of preclinical research performed for this particular lung pathology, we will review existing animal studies and provide suggestions for the development of additional in vivo models of CPFE syndrome. Full article

Given the high risk of lung cancer (LC) in patients with combined pulmonary fibrosis and emphysema (CPFE), and the difficulty of early diagnosis, it is important to understand the impact of LC in these patients. The effect of LC on the development of acute exacerbation (AE) as a natural course of CPFE is still unknown. We retrospectively reviewed medical records of patients at the West China Hospital and enrolled 59 patients with CPFE combined with LC and 68 CPFE patients without LC for initial diagnosis matched in the same period. We compared the clinical characteristics and imaging features of CPFE patients with LC and without LC, and analyzed the associated factors for the prevalence of LC using binary logistic regression. Cox proportional hazards regression analysis was performed to explore risk factors of AE as a natural course of CPFE. Patients with CPFE combined with LC were more common among elderly male smokers. The most common pathological type of tumor was adenocarcinoma (24/59, 40.7%) and squamous cell carcinoma (18/59, 30.5%). Compared with those in the without LC group, the proportions of men, and ex- or current smokers, and the levels of smoking pack-years, serum CRP, IL-6, fibrinogen, complement C3 and C4 in patients with LC were significantly higher (p < 0.05). There was no significant difference in the proportion of natural-course-related AE (10.2% vs. 16.2%, p > 0.05) between the two groups. Logistic regression analysis demonstrated that pack-years ≥ 20 (OR: 3.672, 95% CI: 1.165–11.579), family history of cancer (OR: 8.353, 95% CI: 2.368–10.417), the level of fibrinogen > 4.81 g/L (OR: 3.628, 95% CI: 1.403–9.385) and serum C3 > 1.00 g/L (OR: 5.299, 95% CI: 1.727–16.263) were independently associated with LC in patients with CPFE. Compared to those without AE, CPFE patients with AE had significantly higher levels of PLR and serum CRP, with obviously lower DLCO and VC. The obviously increased PLR (HR: 3.731, 95% CI: 1.288–10.813), and decreased DLCO%pred (HR: 0.919, 95% CI: 0.863–0.979) and VC%pred (HR: 0.577, 95% CI: 0.137–0.918) rather than the presence of LC independently contributed to the development of natural-course-related AE in patients with CPFE. Pack-years, family history of cancer, the levels of fibrinogen and serum C3 were independently associated with LC in patients with CPFE. The presence of LC did not significantly increase the risk of AE as a natural course of CPFE. Clinicians should give high priority to CPFE patients, especially those with more severe fibrosis and systemic inflammation, in order to be alert for the occurrence of AE. Full article

PBT has a unique depth–dose curve with a Bragg peak that enables one to reduce the dose to normal lung tissue. We prospectively enrolled 54 patients with non-small cell lung cancer treated with definitive PBT. The inclusion criteria were forced expiratory volume in 1 s (FEV1) ≤ 1.0 L or FEV1 ≤ 50% of predicted or diffusing capacity of the lungs for carbon monoxide (DLco) ≤ 50%, or pulmonary fibrosis. The primary endpoint was grade ≥ 3 pulmonary toxicity, and secondary endpoints were changes in pulmonary function and quality of life. The median age was 71.5 years (range, 57–87). Fifteen (27.8%) and fourteen (25.9%) patients had IPF and combined pulmonary fibrosis and emphysema, respectively. The median predicted forced vital capacity (FVC), FEV1, and DLco were 77% (range, 42–104%), 66% (range, 31–117%), and 46% (range, 23–94%), respectively. During the follow-up (median, 14.7 months), seven (13.0%) patients experienced grade ≥ 3 pulmonary toxicity. Seven months after the completion of PBT, patients with IPF or non-IPF interstitial lung disease (ILD) experienced a decrease in the FVC but the decrease in DLco was not significant. Under careful monitoring by pulmonologists, PBT could be a useful treatment modality for lung cancer patients with poor lung function or pulmonary fibrosis. Full article

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, fibrosing interstitial lung disease (ILD) of unknown aetiology, with a median survival of 2–4 years from the time of diagnosis. Although IPF has unknown aetiology by definition, there have been identified several risks factors increasing the probability of the onset and progression of the disease in IPF patients such as cigarette smoking and environmental risk factors associated with domestic and occupational exposure. Among them, cigarette smoking together with concomitant emphysema might predispose IPF patients to lung cancer (LC), mostly to non-small cell lung cancer (NSCLC), increasing the risk of lung cancer development. To this purpose, IPF and LC share several cellular and molecular processes driving the progression of both pathologies such as fibroblast transition proliferation and activation, endoplasmic reticulum stress, oxidative stress, and many genetic and epigenetic markers that predispose IPF patients to LC development. Nintedanib, a tyrosine–kinase inhibitor, was firstly developed as an anticancer drug and then recognized as an anti-fibrotic agent based on the common target molecular pathway. In this review our aim is to describe the updated studies on common cellular and molecular mechanisms between IPF and lung cancer, knowledge of which might help to find novel therapeutic targets for this disease combination. Full article

Idiopathic pulmonary fibrosis (IPF) patients have a significantly higher risk of developing lung cancer (LC). There is only limited evidence of the use of texture-based radiomics features from high-resolution computed tomography (HRCT) images for risk stratification of IPF patients for LC. We retrospectively enrolled subjects who suffered from IPF in this study. Clinical data including age, gender, smoking status, and pulmonary function were recorded. Non-contrast chest CT for fibrotic score calculation and determination of three dimensional measures of whole-lung texture and emphysema were performed using a promising deep learning imaging platform. The results revealed that among 116 subjects with IPF (90 non-cancer and 26 lung cancer cases), the radiomics features showed significant differences between non-cancer and cancer patients. In the training cohort, the diagnostic accuracy using selected radiomics features with AUC of 0.66–0.73 (sensitivity of 80.0–85.0% and specificity of 54.2–59.7%) was not inferior to that obtained using traditional risk factors, such as gender, smoking status, and emphysema (%). In the validation cohort, the combination of radiomics features and traditional risk factors produced a diagnostic accuracy of 0.87 AUC and an accuracy of 75.0%. In this study, we found that whole-lung CT texture analysis is a promising tool for LC risk stratification of IPF patients. Full article

Diagnosis of pulmonary hypertension requires a laborious investigation that must be performed in accordance with international Guideliness. Right-heart catheterization is the gold standard examination to assess the degree of hemodynamic impairment of post- or precapillary origin, guiding management. The presence of comorbidities is becoming rather frequent in real-life pulmonary hypertension cases, thus creating diagnostic and therapeutic complexity. We present a case of combined post- and precapillary pulmonary hypertension in a patient with ischemic heart disease and combined pulmonary fibrosis and emphysema, in order to describe the diagnostic algorithm for pulmonary hypertension and elucidate the problematic aspects of managing this debilitating disease in a patient with several comorbidities. Current Guideliness do not support the use of specific vasodilator treatment in group II — due to heart disease and group III-due to lung disease pulmonary hypertension, unless the patient presents with severe pulmonary hypertension (mean pulmonary artery pressure > 35 mm Hg or cardiac index < 2.0 L/min) with right ventricular dysfunction and is treated in an expert center and preferably in the context of a randomized control trial. In the case presented, therapeutic management focused, firstly, on treatment of the underlying heart and lung disease and, subsequently, on specific vasoactive therapy, due to severe hemodynamic deterioration. Full article

Unhealthy lifestyle choices, such as bad eating behaviors and cigarette smoking, have major detrimental impacts on health. However, the inter-relations between obesity and smoking are still not fully understood. We thus developed an experimental model of high-fat diet-fed obese C57BL/6 male mice chronically exposed to cigarette smoke. Our study evaluated for the first time the resulting effects of the combined exposure to unhealthy diet and cigarette smoke on several metabolic, pulmonary, intestinal, and cardiac parameters. We showed that the chronic exposure to cigarette smoke modified the pattern of body fat distribution in favor of the visceral depots in obese mice, impaired the respiratory function, triggered pulmonary inflammation and emphysema, and was associated with gut microbiota dysbiosis, cardiac hypertrophy and myocardial fibrosis. Full article

Combined pulmonary fibrosis and emphysema (CPFE) has been increasingly recognized over the past 10–15 years as a clinical entity characterized by rather severe imaging and gas exchange abnormalities, but often only mild impairment in spirometric and lung volume indices. In this review, we explore the gas exchange and mechanical pathophysiologic abnormalities of pulmonary emphysema, pulmonary fibrosis, and combined emphysema and fibrosis with the goal of understanding how individual pathophysiologic observations in emphysema and fibrosis alone may impact clinical observations on pulmonary function testing (PFT) patterns in patients with CPFE. Lung elastance and lung compliance in patients with CPFE are likely intermediate between those of patients with emphysema and fibrosis alone, suggesting a counter-balancing effect of each individual process. The outcome of combined emphysema and fibrosis results in higher lung volumes overall on PFTs compared to patients with pulmonary fibrosis alone, and the forced expiratory volume in one second (FEV₁)/forced vital capacity (FVC) ratio in CPFE patients is generally preserved despite the presence of emphysema on chest computed tomography (CT) imaging. Conversely, there appears to be an additive deleterious effect on gas exchange properties of the lungs, reflecting a loss of normally functioning alveolar capillary units and effective surface area available for gas exchange, and manifested by a uniformly observed severe reduction in the diffusing capacity for carbon monoxide (D_LCO). Despite normal or only mildly impaired spirometric and lung volume indices, patients with CPFE are often severely functionally impaired with an overall rather poor prognosis. As chest CT imaging continues to be a frequent imaging modality in patients with cardiopulmonary disease, we expect that patients with a combination of pulmonary emphysema and pulmonary fibrosis will continue to be observed. Understanding the pathophysiology of this combined process and the abnormalities that manifest on PFT testing will likely be helpful to clinicians involved with the care of patients with CPFE. Full article

Idiopathic pulmonary fibrosis (IPF) is the most common of the idiopathic interstitial pneumonias. It is characterized by a chronic, progressive, fibrotic interstitial lung disease of unknown cause that occurs primarily in older adults. Its prevalence and incidence have appeared to be increasing over the last decades. Despite its unknown nature, several genetic and environmental factors have been associated with IPF. Moreover, its natural history is variable, but could change depending on the currently suggested phenotypes: rapidly progressive IPF, familial, combined pulmonary fibrosis and emphysema, pulmonary hypertension, and that associated with connective tissue diseases. Early recognition and accurate staging are likely to improve outcomes and induce a prompt initiation of antifibrotics therapy. Treatment is expected to be more effective in the early stages of the disease, while developments in treatment aim to improve the current median survival of 3–4 years after diagnosis. Full article