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Abstract Background Interstitial pneumonia and emphysema may complicate patients with lung cancer. However, clinical significance of trivial and mild pulmonary abnormalities remains unclear. In this study, we aimed to investigate whether trivial and mild interstitial pneumonia and emphysema, in addition to their advanced forms, impact the prognosis and lead to acute exacerbation of interstitial pneumonia (AEIP) in patients with lung cancer. Methods This retrospective cohort study was conducted at a tertiary hospital and included patients with lung cancer. Computed tomography images were evaluated using the interstitial lung abnormality (ILA) score for interstitial pneumonia, which included no ILA, equivocal ILA, ILA, interstitial lung disease (ILD), and the Goddard score for emphysema. Cox analyses were performed using the ILA and Goddard scores as the main explanatory variables, adjusting for multiple covariates. Results Among 1,507 patients with lung cancer, 1,033 had no ILA, 160 had equivocal ILA, 174 had ILA, and 140 had ILD. In total, 474 patients (31.5%) exhibited interstitial pneumonia and 638 (42.3%) showed emphysema. The log-rank trend test showed that survival probability was significantly better in patients with no ILA, followed by those with equivocal ILA, ILA, and ILD (P

Background: Interstitial pneumonia and emphysema may complicate patients with lung cancer. However, clinical significance of trivial and mild pulmonary abnormalities remains unclear. In this study, we aimed to investigate whether trivial and mild interstitial pneumonia and emphysema, in addition to their advanced forms, impact the prognosis and lead to acute exacerbation of interstitial pneumonia (AEIP) in patients with lung cancer. Methods: This retrospective cohort study was conducted at a tertiary hospital and included patients with lung cancer. Computed tomography images were evaluated using the interstitial lung abnormality (ILA) score for interstitial pneumonia, which included no ILA, equivocal ILA, ILA, interstitial lung disease (ILD), and the Goddard score for emphysema. Cox analyses were performed using the ILA and Goddard scores as the main explanatory variables, adjusting for multiple covariates. Results: Among 1,507 patients with lung cancer, 1,033 had no ILA, 160 had equivocal ILA, 174 had ILA, and 140 had ILD. In total, 474 patients (31.5%) exhibited interstitial pneumonia and 638 (42.3%) showed emphysema. The log-rank trend test showed that survival probability was significantly better in patients with no ILA, followed by those with equivocal ILA, ILA, and ILD (P < 0.001). After adjustment, the ILA and Goddard scores remained significant variables for increased hazard ratios (HR) for mortality: no ILA (HR, 1.00: reference), equivocal ILA (HR, 1.31; 95% confidence interval [CI], 1.18–1.46; P < 0.001), ILA (HR, 1.71; 95% CI, 1.39–2.12; P < 0.001), ILD (HR, 2.24; 95% CI, 1.63–3.09; P < 0.001), and Goddard score (HR, 1.03; 95% CI, 1.01–1.06; P < 0.010). Moreover, both scores were associated with increased cause-specific HRs for AEIP. Conclusion: Our results revealed that approximately one-third of patients with lung cancer had interstitial pneumonia when incorporating trivial and mild cases. Because interstitial pneumonia and emphysema, ranging from trivial to severe, significantly impact mortality and AEIP in patients with lung cancer, we should identify even trivial and mild cases of these pulmonary abnormalities among patients with lung cancer in addition to the advanced ones. [ABSTRACT FROM AUTHOR]

This article presents a case study of a 78-year-old man who experienced a worsening of respiratory symptoms after taking the medication loxoprofen for knee pain. The patient was diagnosed with acute exacerbation of combined pulmonary fibrosis and emphysema (CPFE) due to suspected loxoprofen-induced lung injury. While loxoprofen is commonly used to treat arthritis and inflammation, the development of interstitial pneumonia is rare. Treatment with corticosteroids resulted in improvement for the patient. The authors emphasize the importance of considering drug-induced lung injury as a potential cause of acute exacerbation in patients with CPFE. This information may be valuable for researchers and healthcare professionals studying or treating CPFE and drug-induced lung injury. [Extracted from the article]

Background: Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive fibrosing interstitial lung disease. The effects of emphysema on mortality in IPF remains unclear. Methods: MEDLINE, Embase and Cochrane Library databases were searched. Studies were included if they compared mortality in IPF patients with and without emphysema. In included studies, the diagnosis with IPF or IPF combined emphysema was according to the ATS and ERS statements. From eligible studies, we extracted HR and 95% CI, if HRs were not reported, they were extracted based on Kaplan–Meier curves. Results: A total of 2605 patients across 15 cohort studies were included in the systematic review and meta-analysis. Emphysema was associated with increased risk of all-cause mortality with a pooled HR 1.37 (95% CI, 1.04-1.80) and I 2 = 64%. However, the level of evidence was 'very low' according to GRADE criteria. Subgroup analysis according to IPF with emphysema patients revealed that DLCO%pre<40 (HR 1.75 (95% CI, 1.02-3.01) and I 2 = 74%), FVC%pre<80 (HR 1.81 (95% CI, 1.24-2.64) and I 2 = 61%), location on North America and Europe (HR 2.00 (95% CI, 1.09-3.67) and I 2 = 76%), and Smoking Pack-years<40 (HR 1.38 (95% CI, 1.02-1.87) and I 2 = 15%) were risk factors for all-cause mortality. Sensitivity analysis revealed that one study had a disproportional effect on the pooled rate. Conclusions: Our findings suggested emphysema increased the risk of all-cause mortality in patients with IPF. This conclusion should be re-evaluated by a large-scale randomized controlled trial. Trial Registration: PROSPERO: CRD42022378699; https://www.crd.york.ac.uk/prospero/. [ABSTRACT FROM AUTHOR]

Pulmonary hypertension (PH) results in increased morbidity and mortality in patients with interstitial lung disease (ILD). Early recognition of PH in this population is essential for planning diagnostic testing, initiating therapy, and evaluating for lung transplantation. The previously developed PH-ILD Detection tool has significant potential in the evaluation and treatment of ILD patients; the aim of this study was to validate the tool in an independent, multicenter cohort of patients. We conducted a retrospective review of prospectively collected data from 161 ILD patients. Patients were stratified into low- (n = 78, 48.4%), intermediate- (n = 54, 33.5%), and high-risk (n = 29, 18.0%) groups based on the score obtained with the tool. Intermediate- and high-risk patients underwent follow-up echocardiogram (TTE); 49.4% (n = 41) had an abnormal TTE suggestive of underlying PH. These patients underwent right heart catheterization; PH-ILD was diagnosed in 73.2% (n = 30) of these cases. The PH-ILD Detection tool has a sensitivity of 93.3%, specificity of 90.9%, and area-under-the-curve of 0.921 for diagnosing PH in ILD patients, validating the findings from the original study and establishing the tool as a fundamental resource for early recognition of PH in ILD patients. [ABSTRACT FROM AUTHOR]

Combined pulmonary fibrosis and emphysema (CPFE) is a heterogenous lung disease documented in smokers, which includes emphysema in upper lobes and pulmonary fibrosis in lower lobes. CPFE in nonsmokers is rare, and very few literatures are available. In this case report, we have reported an 80-year-old male presented with progressive shortness of breath with fatigability and hypoxia treated as emphysema with inhaled bronchodilators. Response to medical treatment was not satisfactory with worsening of shortness of breath and fatigability. Clinical examination revealed bilateral basal velcro crepitations with resting oxygen saturation was 88% at room air. High-resolution computerized imaging documented emphysema in upper lobes with honeycombing and tractional bronchiectasis in lower lobes. Echocardiography documented pulmonary hypertension with dilated right atrium and ventricle. Connective tissue disease (CTD) panel documented workup positive for polymyositis. We have treated with oxygen supplementation during rest and ambulation, long-acting inhaled bronchodilator medicines, antifibrotic nintedanib, anti-inflammatory methylprednisolone, and pulmonary vasodilator tadalafil. Improvement in cardiopulmonary parameters including in 6-minute walk distance was significant with bronchodilators, mycophenolate mofetil, tadalafil, and antifibrotics.

A 59-year-old man who had smoked for 23 pack-years was admitted to our hospital because of two-month history of back pain. The chest computed tomography scan demonstrated combined pulmonary fibrosis and emphysema (CPFE) and an irregular shaped nodule in the left lower lobe of the lung. A biopsy obtained from samples from subcarinal lymph nodes revealed non-small cell lung cancer. Anti-aminoacyl-tRNA synthetase (ARS) antibody was elevated up to 166 U/mL, although he had no symptoms suggestive connective tissue diseases. It is well known that most of CPFE patients are current or former heavy smokers, and some researchers described the relationship between CPFE and connective tissue diseases. To our best knowledge, this was the first report of lung cancer in patient with anti-ARS antibody-positive CPFE. In some anti-ARS antibody-positive patients, smoking might have a relationship with development of CPFE and lung cancer.

Abstract Pulmonary hypertension (PH) results in increased morbidity and mortality in patients with interstitial lung disease (ILD). Early recognition of PH in this population is essential for planning diagnostic testing, initiating therapy, and evaluating for lung transplantation. The previously developed PH‐ILD Detection tool has significant potential in the evaluation and treatment of ILD patients; the aim of this study was to validate the tool in an independent, multicenter cohort of patients. We conducted a retrospective review of prospectively collected data from 161 ILD patients. Patients were stratified into low‐ (n = 78, 48.4%), intermediate‐ (n = 54, 33.5%), and high‐risk (n = 29, 18.0%) groups based on the score obtained with the tool. Intermediate‐ and high‐risk patients underwent follow‐up echocardiogram (TTE); 49.4% (n = 41) had an abnormal TTE suggestive of underlying PH. These patients underwent right heart catheterization; PH‐ILD was diagnosed in 73.2% (n = 30) of these cases. The PH‐ILD Detection tool has a sensitivity of 93.3%, specificity of 90.9%, and area‐under‐the‐curve of 0.921 for diagnosing PH in ILD patients, validating the findings from the original study and establishing the tool as a fundamental resource for early recognition of PH in ILD patients.

Although chronic obstructive pulmonary disease (COPD) and interstitial lung disease (ILD) have distinct clinical features, both diseases may coexist in a patient because they share similar risk factors such as smoking, male sex, and old age. Patients with both emphysema in upper lung fields and diffuse ILD are diagnosed with combined pulmonary fibrosis and emphysema (CPFE), which causes substantial clinical deterioration. Patients with CPFE have higher mortality compared with patients who have COPD alone, but results have been inconclusive compared with patients who have idiopathic pulmonary fibrosis (IPF). Poor prognostic factors for CPFE include exacerbation, lung cancer, and pulmonary hypertension. The presence of interstitial lung abnormalities, which may be an early or mild form of ILD, is notable among patients with COPD, and is associated with poor prognosis. Various theories have been proposed regarding the pathophysiology of CPFE. Biomarker analyses have implied that this pathophysiology may be more closely associated with IPF development, rather than COPD or emphysema. Patients with CPFE should be advised to quit smoking and undergo routine lung function tests, and pulmonary rehabilitation may be helpful. Various pharmacologic agents and surgical approaches may be beneficial in patients with CPFE, but further studies are needed.

A 60-year-old male smoker came with dyspnea. A rare condition known as combined pulmonary fibrosis and emphysema (CPFE) was observed on a chest CT scan. Decreased DLCO in combination with normal FVC can help diagnose CPFE. Concomitant connective tissue diseases, including rheumatoid arthritis, should be checked in CPFE patients., Competing Interests: There is no conflict of interest., (© 2024 The Author(s). Clinical Case Reports published by John Wiley & Sons Ltd.)

Objective: To determine the incidence and predictive factors of lung cancer in rheumatoid arthritis (RA)., Methods: We conducted a retrospective follow-up study of patients who were diagnosed with RA at our institution between April 2001 and December 2022. Pulmonary complications were evaluated using high-resolution computed tomography at RA diagnosis. Patients were followed until the diagnosis of lung cancer, diagnosis of other malignancies, death, loss to follow-up, or the end of the study., Results: Among 771 RA patients, 3.5% were diagnosed with combined pulmonary fibrosis and emphysema (CPFE), 4.9% with interstitial lung disease (ILD) alone, and 6.0% with emphysema alone. During follow-up (mean of 9.3 years), the crude incidence rates of lung cancer per 1,000 patient-years were 2.9 in all patients, 47.8 in CPFE patients, 10.5 in ILD patients, 11.9 in emphysema patients, and 0.8 in patients without these complications. The standardized incidence ratios (95% confidence intervals [CI]) compared with the general population were 2.53 (1.29-3.77) for male patients and 0.89 (0.57-1.16) for female patients. In Fine-Gray regression analysis, adjusted hazard ratios (95% CI) of lung cancer were 13.48 (3.14-57.85) for CPFE, 6.42 (1.42-29.09) for ILD alone, and 4.65 (1.18-18.30) for emphysema alone versus without these complications, and 1.02 (1.01-1.04) per additional 1 pack-year for smoking history. These factors were not associated with the risk of other malignancies., Conclusion: Close monitoring of lung cancer is needed for RA patients with smoking history and pulmonary complications, especially CPFE., (© Japan College of Rheumatology 2024. Published by Oxford University Press.)

Aim: Combined pulmonary fibrosis and emphysema (CPFE) and idiopathic pulmonary fibrosis (IPF) have been discussed intensively in recent years as two different entities. We aimed to compare the clinical, functional and respiratory parameters, clinical course and mortality rates of patients with CPFE and IPF. Materials and Methods: 36 patients with a diagnosis of CPFE and 40 IPF who applied between September 2013 and February 2019 were retrospectively included in the study. Demographic data, comorbidities, pulmonary function parameters, mortality, systolic pulmonary artery pressures(sPAP) recorded. Results: In the CPFE patient group, the ratio of male patients (p=0.02), smoking history (p=0.00), frequency of acute exacerbation (p=0.001) were found to be significantly higher, SF-36 total score (p=0.000) were significantly lower than IPF group. While FVC% (p=0.00), FEV1% (p=0.049) and TLC% (p=0.002) were significantly higher in the CPFE group than IPF group, TLCO% (p=0.002) and FEV1/FVC (p=0.00) was lower. Pulmonary hypertension (PH) was 40% in CPFE and 37% in IPF and no significant difference was found between them (p=0.806). Those who received long-term oxygen therapy (LTOT) were more common in the CPFE group (p=0.04). In CPFE patients; the percentage of those who treated with bronchodilator, antifibrotic, systemic corticosteroid was respectively 52.7%, 36.1%, 5.6%. Mortality from any cause was 9(25%) in CPFE and 8(20%) in IPF, and there was no significant difference between the two groups (p=0.601). Conclusion: It was observed that lung volumes were preserved and gas exchange of the lung was significantly decreased in patients with CPFE. Compared to IPF, the quality of life was lower and acute exacerbation was more common in CPFE. The frequency of PH and mortality were similar in both groups. Male gender and smoking history were important risk factors for CPFE patients. There is a need for multicenter studies reporting the clinical features, prognosis, and mortality of CPFE. [ABSTRACT FROM AUTHOR]

Abstract Rationale Patients with combined pulmonary fibrosis and emphysema (CPFE) may develop acute exacerbations of IPF (AE-IPF) or COPD (AE-COPD). The incidence and the characteristics of exacerbations in patients with CPFE (e.g., COPD vs IPF) have not been well described. Objectives To compare the incidence and rate of exacerbations in patients with CPFE vs. IPF and evaluate their effect on clinical outcomes. Methods Comprehensive clinical data from CPFE and IPF patients were retrospectively reviewed. Baseline characteristics including lung function data, oxygen requirements, and pulmonary hemodynamics, were collected. Acute exacerbation events in both groups were defined clinically and radiographically. In the CPFE group, two patterns of exacerbations were identified. AE-COPD was defined clinically by symptoms of severe airflow obstruction causing respiratory failure and requiring hospitalization. Radiographic data were also defined based on previously published literature. AE-IPF was defined clinically as an acute hypoxic respiratory failure, requiring hospitalization and treatment with high dose corticosteroids. Radiographically, patients had to have a change in baseline imaging including presence of ground-glass opacities, interlobular septal thickening or new consolidations; that is not fully explained by other etiologies. Results Eighty-five CPFE patients were retrospectively compared to 112 IPF patients. Of 112 patients with IPF; 45 had AE-IPF preceding lung transplant (40.18%) compared to 12 patients in the CPFE group (14.1%) (p

Abstract Background Previous analyses of combined pulmonary fibrosis and emphysema (CPFE) cohorts have provided conflicting data on the survival of patients with CPFE. Therefore, the aim of this study was to investigate the clinical prognosis of acute exacerbations (AE) of CPFE. Methods We retrospectively reviewed the medical records of patients who had been treated at the Shinshu University Hospital (Matsumoto, Japan) between 2003 and 2017. We identified 21 patients with AE of CPFE and 41 patients with AE of idiopathic pulmonary fibrosis (IPF) and estimated their prognoses using the Kaplan–Meier method. Results Treatment content and respiratory management were not significantly different between the two groups before and after exacerbation. At the time of AE, the median serum Krebs von den Lungen-6 level was significantly lower in the CPFE group (Krebs von den Lungen-6: 966 U/μL; white blood cell count: 8810 /μL) than that in the IPF group (Krebs von den Lungen-6: 2130 U/μL, p

Topic Importance: Combined pulmonary fibrosis and emphysema (CPFE) is an underdiagnosed syndrome in which individuals have variable degrees of pulmonary fibrosis and emphysema. Patients with CPFE have high morbidity, including poor exercise tolerance and increased development of comorbidities. CPFE mortality also seems to outpace that of lone emphysema and pulmonary fibrosis. A major limitation to rigorous, large-scale studies of CPFE has been the lack of a precise definition for this syndrome. A 2022 American Thoracic Society/European Respiratory Society/Japanese Respiratory Society/Latin American Thoracic Association Research Statement called attention to fundamental gaps in our understanding of CPFE and highlighted the potential use of quantitative imaging techniques to better define CPFE., Review Findings: Broadly, CPFE has been defined using visual interpretation of chest CT imaging documenting the presence of both emphysema and fibrosis, with varying distributions. When quantitative approaches were involved, varying thresholds of emphysema and fibrosis on imaging have been used across different studies., Summary: This review is structured into three primary themes, starting with early imaging studies, then evaluating the use of quantitative methods and imaging-based thresholds, both in large population studies and single-center cohorts to define CPFE and assess patient outcomes. It concludes by discussing current challenges and how to focus our efforts so that quantitative imaging methods can effectively address the most pressing clinical dilemmas in CPFE., Competing Interests: Financial/Nonfinancial Disclosures The authors have reported to CHEST the following: J. M. O. reports consulting fees from Boehringer Ingelheim, Lupin Pharmaceuticals, AmMax Bio, Roche, and Veracyte; personal fees from Endeavor Biomedicines, Novartis, and Genentech; leadership roles in CHEST, the American Thoracic Society, and the American Journal of Respiratory and Critical Care Medicine; and stock options in Gatehouse Bio. M. K. H. reports personal fees from GlaxoSmithKline, AstraZeneca, Boehringer Ingelheim, Cipla, Chiesi, Novartis, Pulmonx, Teva, Verona, Merck, Mylan, Sanofi, Roche, DevPro, Aerogen, Polarian, Regeneron, Amgen, Genentech, UpToDate, Altesa Biopharma, Apreo Health, RS Biotherapeutics, Medscape, NACE, MDBriefCase, Integrity, and MedWiz. She has received either in kind research support or funds paid to the institution from the National Institutes of Health, Novartis, Sunovion, Nuvaira, Sanofi, AstraZeneca, Boehringer Ingelheim, Gala Therapeutics, Biodesix, the COPD Foundation, and the American Lung Association; has participated in Data and Safety Monitoring Boards for Novartis and Medtronic with funds paid to the institution; and has received stock options from Meissa Vaccines and Altesa Biopharma. V. C. reports consulting fees from AstraZeneca, Boehringer Ingelheim, BMS, CSL, Ferrer, GSK, Pliant, PureTech, RedX, Roche, Sanofi, Shionogi, and Vifor; lecture fees from Astra Zeneca, Boehringer Ingelheim, Ferrer, Roche, and Sanofi; travel support from Boehringer Ingelheim and Sanofi; committee role for FibroGen; and participation in Data and Safety Monitoring Boards for Galapagos, Galecto, GSK and Molecure. None declared (J. M. W., T. A.)., (Copyright © 2024 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Diagnosis and treatment of patients with smoking-related lung diseases often requires multidisciplinary contributions to optimize care. Imaging plays a key role in characterizing the underlying disease, quantifying its severity, identifying potential complications, and directing management. The primary goal of this article is to provide an overview of the imaging findings and distinguishing features of smoking-related lung diseases, specifically, emphysema/chronic obstructive pulmonary disease, respiratory bronchiolitis-interstitial lung disease, smoking-related interstitial fibrosis, desquamative interstitial pneumonitis, combined pulmonary fibrosis and emphysema, pulmonary Langerhans cell histiocytosis, and E-cigarette or vaping related lung injury., Competing Interests: Disclosure The authors have nothing to disclose., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Combined pulmonary fibrosis and emphysema (CPFE) is recognized as a characteristic syndrome of smoking-related interstitial lung disease that has a worse prognosis than idiopathic pulmonary fibrosis (IPF). However, outcomes after lung transplantation for CPFE have not been reported. The aim of this study is to describe the clinical features and outcomes of CPFE after lung transplantation.Research Question: What are the clinical features and outcomes of CPFE after lung transplantation?Study Design and Methods: This is a single-center retrospective cohort study of patients with CPFE and IPF who underwent lung transplantation at our center between January 2011 and December 2016. We defined CPFE as ≥10% emphysema in the upper lung fields combined with fibrosis on high-resolution CT scan. We characterized the clinical features of patients with CPFE and compared their outcomes after lung transplantation with those with IPF.Results: Twenty-seven of 172 (16%) patients with IPF met criteria for CPFE. Severe pulmonary hypertension was present in 16 of 27 (59%) patients with CPFE. On logistic regression analysis, CPFE was significantly associated with primary graft dysfunction (PGD) grade 3 (OR, 3.14; 95% CI, 1.18-8.37; P = .02). On competing risk regression analysis, CPFE was associated with acute cellular rejection (ACR) grade ≥ A2, and chronic lung allograft dysfunction (CLAD) (hazard ratio [HR], 1.89; 95% CI, 1.10-3.25; P = .02; HR, 1.96; 95% CI, 1.02-3.77; P = .04, respectively). Five-year survival was 79.0% for the CPFE group and 75.4% for the IPF group (log-rank P = .684).Interpretation: After transplantation, patients with CPFE were more likely to develop PGD, ACR, and CLAD compared with those with IPF. However, survival was not significantly different between the two groups. [ABSTRACT FROM AUTHOR]

Riociguat in Patients with Symptomatic Pulmonary Hypertension associated with Idiopathic Interstitial Pneumonias (RISE-IIP), a randomized, controlled, phase 2b trial of riociguat for pulmonary hypertension associated with idiopathic interstitial pneumonia, was terminated early due to increased mortality in riociguat-treated patients. Baseline characteristics of enrolled patients demonstrated a low diffusing capacity of the lung for carbon monoxide (DL CO) with preserved lung volumes at baseline, suggesting the presence of combined pulmonary fibrosis and emphysema (CPFE) in some patients. This post hoc analysis of RISE-IIP was undertaken to explore lung morphology, assessed by high-resolution computed tomography, and associated clinical outcomes. Available baseline/pre-baseline high-resolution computed tomography scans were reviewed centrally by 2 radiologists. The extent of emphysema and fibrosis was retrospectively scored and combined to provide the total CPFE score. Data were available for 65/147 patients (44%), including 15/27 fatal cases (56%). Of these, 41/65 patients (63%) had CPFE. Mortality was higher in patients with CPFE (12/41; 29%) than those without (3/24; 13%). Fourteen patients with CPFE had emphysema > fibrosis (4 died). No relationship was observed between CPFE score, survival status, and treatment assignment. A low DL CO , short 6-min walking distance, and high forced vital capacity:DL CO ratio at baseline also appeared to be risk factors for mortality. High parenchymal lung disease burden and the presence of more emphysema than fibrosis might have predisposed patients with pulmonary hypertension associated with idiopathic interstitial pneumonia to poor outcomes in RISE-IIP. Future studies of therapy for group 3 pulmonary hypertension should include centrally adjudicated imaging for morphologic phenotyping and disease burden evaluation during screening. [ABSTRACT FROM AUTHOR]

Background: Lung cancer is an important complication of combined pulmonary fibrosis and emphysema (CPFE). Whether the risk of lung cancer is higher in CPFE patients with usual interstitial pneumonia (UIP) than those with idiopathic pulmonary fibrosis (IPF) alone, remains controversial. We conducted this systematic review and meta-analysis to evaluate the prevalence of lung cancer in CPFE patients with UIP compared with IPF patients. Methods: We searched the PubMed, Embase, and Cochrane databases for studies that focused on the incidence of lung cancer in CPFE/UIP and IPF groups. We used a fixed-effects model to analyze the odds ratios (ORs) with 95% confidence intervals (CIs) according to data heterogeneity. The cumulative effects based on the publication year and sample size were assessed by cumulative meta-analysis. Results: A total of nine studies with 933 patients, including 374 CPFE patients with UIP, fulfilled the inclusion criteria. Overall, CPFE patients with UIP have a higher risk of lung cancer than those with IPF alone (OR = 2.69; 95% CI: 1.78–4.05). There were increased risks of lung cancer in CPFE/UIP patients with the presence of emphysema (OR = 2.93; 95% CI: 1.79–4.79) or emphysema in ⩾10% of the lung volume (OR = 2.22; 95% CI: 1.06–4.68). Conclusions: Our systematic review and meta-analysis indicated a significantly higher prevalence of lung cancer in CPFE patients with UIP than in patients with IPF alone. The reviews of this paper are available via the supplemental material section. [ABSTRACT FROM AUTHOR]

Background: Combined pulmonary fibrosis and emphysema (CPFE) is a distinct entity among fibrosing lung diseases with a high risk for lung cancer and pulmonary hypertension (PH). Notably, concomitant PH was identified as a negative prognostic indicator that could help with early diagnosis to provide important information regarding prognosis. Objectives: The current study aimed to determine whether cardiopulmonary exercise testing (CPET) can be helpful in differentiating patients having CPFE with and without PH. Methods: Patients diagnosed with CPFE in 2 German cities (Hemer and Greifswald) over a period of 10 years were included herein. CPET parameters, such as peak oxygen uptake (peak VO2), functional dead space ventilation (VDf/VT), alveolar-arterial oxygen difference (AaDO2), arterial-end-tidal CO2 difference [P(a-ET)CO2] at peak exercise, and the minute ventilation-carbon dioxide production relationship (VE/VCO2 slope), were compared between patients with and without PH. Results: A total of 41 patients with CPET (22 with PH, 19 without PH) were analyzed. Right heart catheterization was performed in 15 of 41 patients without clinically relevant complications. Significant differences in peak VO2 (861 ± 190 vs. 1,397 ± 439 mL), VO2/kg body weight/min (10.8 ± 2.6 vs. 17.4 ± 5.2 mL), peak AaDO2 (72.3 ± 7.3 vs. 46.3 ± 14.2 mm Hg), VE/VCO2 slope (70.1 ± 31.5 vs. 39.6 ± 9.6), and peak P(a-ET)tCO2 (13.9 ± 3.5 vs. 8.1 ± 3.6 mm Hg) were observed between patients with and without PH (p < 0.001). Patients with PH had significantly higher VDf/VT at rest, VT1, and at peak exercise (65.6 ± 16.8% vs. 47.2 ± 11.6%; p < 0.001) than those without PH. A cutoff value of 44 for VE/VCO2 slope had a sensitivity and specificity of 94.7 and 72.7%, while a cutoff value of 11 mm Hg for P(a-ET)CO2 in combination with peak AaDO2 >60 mm Hg had a specificity and sensitivity of 95.5 and 84.2%, respectively. Combining peak AaDO2 >60 mm Hg with peak VO2/body weight/min <16.5 mL/kg/min provided a sensitivity and specificity of 100 and 95.5%, respectively. Conclusion: This study provided initial data on CPET among patients having CPFE with and without PH. CPET can help noninvasively detect PH and identify patients at risk. AaDO2 at peak exercise, VE/VCO2 slope, peak P(a-ET)CO2, and peak VO2 were parameters that had high sensitivity and, when combined, high specificity. [ABSTRACT FROM AUTHOR]

Mucins have long been regarded to play a role as a barrier to prevent mucosal infections; however, some studies report that overexpression of mucins induces obstruction and inflammation of airways. We investigated whether the secretion of overexpressed mucin, mucin5ac (MUC5AC), could improve protection against pathogens. To examine the possible roles of mucin hypersecretion in augmenting host defense against disease‐promoting muco‐obstructive lung disease, a mouse model that overexpressed MUC5AC was generated. We had previously proved that murine gammaherpesvirus‐68 (MHV‐68) infection could induce emphysema in mice, which later developed into combined pulmonary fibrosis and emphysema (CPFE). We further explored whether increased MUC5AC secretion could provide benefits against MHV‐68 induced fibrosis. We initially developed a pcDNA3.1‐MUC5AC mouse model. Next, the experimental mice were randomly divided into five groups: normal control, pcDNA3.1 control, pcDNA3.1‐MUC5AC, CPFE, and pcDNA3.1‐ MUC5AC + CPFE. Morphometric analysis of each group was performed by hematoxylin and eosin staining and Masson trichrome staining. MUC5AC levels in lung tissues were analyzed by immunohistochemical staining, real‐time polymerase chain reaction, and Western blot analysis. The airway inflammation was determined by differential cell counts of bronchoalveolar lavage fluid (BALF) and measurement of cytokines and chemokines in BALF by enzyme‐linked immunosorbent assay. MUC5AC hypersecretion alone was not sufficient to drive goblet cell metaplasia to induce obvious mucus plugging and airway inflammation. However, MUC5AC overexpression served as a protective barrier against MHV‐68 virus infection in vivo. Infectivity of MHV‐68 was decreased in the pcDNA3.1‐MUC5AC + CPFE group compared with that in CPFE group. Meanwhile, a reduction of MHV‐68 virus attenuated the expressions of chemokine (C‐C motif) ligand 2 (CCL2), chemokine (C‐X‐C motif) ligand 5 (CXCL5), interleukin‐13 (IL‐13), and transforming growth factor‐β1 (TGF‐β1), and weakened airway inflammation and fibrosis in the pcDNA3.1‐MUC5AC + CPFE group. Overexpression of MUC5AC appears to exhibit a protective role against MHV‐68 infection in mice with emphysema that subsequently developed into CPFE and to further decrease airway inflammation and fibrosis induced by MHV‐68 by decreasing the expressions of CCL2, CXCL5, IL‐13, and TGF‐β1. Highlights: Overexpression of MUC5AC appears to further decrease airway inflammation and fibrosis induced by MHV‐68 by decreasing the expressions of CCL2, CXCL5, IL‐13, and TGF‐β1. [ABSTRACT FROM AUTHOR]

Open in new tab Download slide Open in new tab Download slide OBJECTIVES Lung cancer treatment in patients with chronic lung diseases is challenging because postoperative care is difficult and surgical outcomes are poorer than in patients with healthy lungs. This study aimed to examine postsurgical outcomes of patients with comorbid lung diseases treated for lung cancer. METHODS This retrospective study enrolled 1526 patients who underwent curative surgical resection for non-small-cell lung cancer at a single centre between October 2008 and April 2017. Based on computed tomography findings, patients were assigned to 4 groups and their demographic characteristics, clinicopathological features, surgical outcomes and survival were compared. RESULTS There were 1101 patients in group A, 266 patients in group B, 62 patients in group C and 97 patients in group D. In the chronic lung disease groups (B, C and D), there was a high percentage of smoking history (86.5%, 79.0% and 92.8%, respectively; P  < 0.01). The occurrence rate of postoperative lung complications and operative mortality rates were higher in patients with chronic lung disease. Groups A, B, C and D contained 819 (74.4%), 159 (59.8%), 43 (69.4%) and 65 (67.0%) stage I patients, respectively (P  < 0.01). The groups showed significant differences in overall survival and disease-free survival (all P  < 0.01). The presence of combined pulmonary fibrosis and emphysema was the only significant negative prognostic factor for overall survival. CONCLUSIONS The presence of comorbid chronic lung diseases might negatively affect prognosis in patients with non-small-cell lung cancer. The presence of combined pulmonary fibrosis and emphysema could be a negative prognostic factor in lung cancer treatment. [ABSTRACT FROM AUTHOR]

Rationale: Patients with combined pulmonary fibrosis and emphysema (CPFE) may develop acute exacerbations of IPF (AE-IPF) or COPD (AE-COPD). The incidence and the characteristics of exacerbations in patients with CPFE (e.g., COPD vs IPF) have not been well described.Objectives: To compare the incidence and rate of exacerbations in patients with CPFE vs. IPF and evaluate their effect on clinical outcomes.Methods: Comprehensive clinical data from CPFE and IPF patients were retrospectively reviewed. Baseline characteristics including lung function data, oxygen requirements, and pulmonary hemodynamics, were collected. Acute exacerbation events in both groups were defined clinically and radiographically. In the CPFE group, two patterns of exacerbations were identified. AE-COPD was defined clinically by symptoms of severe airflow obstruction causing respiratory failure and requiring hospitalization. Radiographic data were also defined based on previously published literature. AE-IPF was defined clinically as an acute hypoxic respiratory failure, requiring hospitalization and treatment with high dose corticosteroids. Radiographically, patients had to have a change in baseline imaging including presence of ground-glass opacities, interlobular septal thickening or new consolidations; that is not fully explained by other etiologies.Results: Eighty-five CPFE patients were retrospectively compared to 112 IPF patients. Of 112 patients with IPF; 45 had AE-IPF preceding lung transplant (40.18%) compared to 12 patients in the CPFE group (14.1%) (p < 0.05). 10 patients in the CPFE group experienced AE-COPD (11.7%). Patients with AE-IPF had higher mortality and more likely required mechanical ventilation and extracorporeal membrane oxygenation (ECMO) compared to patients with AE-COPD, whether their underlying disease was IPF or CPFE.Conclusions: CPFE patients may experience either AE-IPF or AE-COPD. Patients with CPFE and AE-COPD had better outcomes, requiring less intensive therapy compared to patients with AE-IPF regardless if underlying CPFE or IPF was present. These data suggest that the type of acute exacerbation, AE-COPD vs AE-IPF, has important implications for the treatment and prognosis of patients with CPFE. [ABSTRACT FROM AUTHOR]

Background: Previous analyses of combined pulmonary fibrosis and emphysema (CPFE) cohorts have provided conflicting data on the survival of patients with CPFE. Therefore, the aim of this study was to investigate the clinical prognosis of acute exacerbations (AE) of CPFE.Methods: We retrospectively reviewed the medical records of patients who had been treated at the Shinshu University Hospital (Matsumoto, Japan) between 2003 and 2017. We identified 21 patients with AE of CPFE and 41 patients with AE of idiopathic pulmonary fibrosis (IPF) and estimated their prognoses using the Kaplan-Meier method.Results: Treatment content and respiratory management were not significantly different between the two groups before and after exacerbation. At the time of AE, the median serum Krebs von den Lungen-6 level was significantly lower in the CPFE group (Krebs von den Lungen-6: 966 U/μL; white blood cell count: 8810 /μL) than that in the IPF group (Krebs von den Lungen-6: 2130 U/μL, p < 0.001; white blood cells: 10809/μL, p = 0.0096). The baseline Gender-Age-Physiology scores were not significantly different between the two groups (CPFE, 4.5 points; IPF, 4.7 points; p = 0.58). Kaplan-Meier curves revealed that the survival time after AE for patients with CPFE was longer than that for patients with IPF (p < 0.001, log-rank test).Conclusions: Survival prognoses after AE were significantly better for patients with CPFE than that for those with IPF. Our findings may improve the medical treatment and respiratory management of patients with AE-CPFE. [ABSTRACT FROM AUTHOR]

Background: Combined pulmonary fibrosis and emphysema (CPFE) is a syndrome characterized by the coexistence of upper lobe emphysema and lower lobe fibrosis. However, whether CPFE has a higher or lower mortality than idiopathic pulmonary fibrosis (IPF) alone is still not clear. In this study we conducted a meta-analysis to assess the survival rate (SR) of CPFE versus IPF alone in clinical trials. Methods: We performed a systematic search of PubMed, Embase, and the Cochrane Central Register of Controlled Trials for trials published prior to 31 March 2018. Extracts from the literature were analyzed with Review Manager version 5.3. Results: Thirteen eligible trials were included in this analysis (involving 1710 participants). Overall, the pooled results revealed that no statistically significant difference was detected in the 1-year [relative risk (RR) = 0.98, 95% confidence interval (CI): 0.94–1.03, p = 0.47], 3-year (RR = 0.83, 95% CI: 0.68–1.01, p = 0.06), and 5-year (RR = 0.80, 95% CI: 0.59–1.07, p = 0.14) SRs of CPFE versus IPF alone. Conclusions: CPFE exhibits a very poor prognosis, similar to IPF alone. Additional studies are needed to provide more convincing data to investigate the natural history and outcome of patients with CPFE in comparison to IPF. The reviews of this paper are available via the supplemental material section. [ABSTRACT FROM AUTHOR]

Combined pulmonary fibrosis and emphysema (CPFE) has emerged as a new syndrome with characteristics of both fibrosis and emphysema. We determined the impacts of radiologic emphysema severity on pulmonary function tests (PFTs), exercise capacity and mortality. IPF patients (n = 110) diagnosed at the Chest Diseases Clinic between September 2013 and January 2016 were enrolled in the study and followed up until June 2017. Visual and digital emphysema scores, PFTs, pulmonary artery pressure (sPAP), 6-minute walking test, composite physiologic index (CPI), and survival status were recorded. Patients with emphysema and those with pure IPF were compared. The CPFE-group had a significantly greater ratio of men(p < 0.001), lower BMI (p < 0.001), lower mean PaO 2 (p = 0.005), higher mean sPAP (p = 0.014), and higher exercise desaturation (p < 0.001). The CPFE group had a significantly higher FVC(L)(p = 0.016), and lower FEV1/FVC ratio (p = 0.002), DLCO, and DLCO/VA ratio(p = 0.03 and p = 0.005, respectively). Lung volumes of the CPFE group had significantly higher VC(p = 0.017), FRC (p < 0.001), RV(p < 0.001), RV/TLC(p < 0.001), and TLC(p < 0.001). There were significant correlations between emphysema scores and FVC (L)(p = 0.01), FEV1/FVC(p = 0.001), DLCO (p = 0.003), VC(p = 0.014), FRC (L)(p < 0.001), RV(p < 0.001), TLC(p < 0.001), and RV/TLC (p < 0.001). Mortality rates were comparable between the two groups. CPI (p = 0.02) and sPAP (p = 0.01) were independent predictors of mortality in patients with CPFE. The presence and severity of emphysema affects pulmonary function in IPF. Patients with CPFE have reduced diffusion capacity, more severe air trapping, worse muscle weakness, more severe exercise desaturation, and pulmonary hypertension. CPI and pulmonary hypertension are two independent risk factors for mortality in subjects with CPFE. [ABSTRACT FROM AUTHOR]

The syndrome of combined pulmonary fibrosis and emphysema (CPFE) primarily due to tobacco smoking has been reported in connective tissue disease, but little is known about its characteristics in systemic sclerosis (SSc). In this retrospective multi-center case-control study, we identified 36 SSc patients with CPFE, and compared them with 72 SSc controls with interstitial lung disease (ILD) without emphysema. Rate of CPFE in SSc patients with CT scan was 3.6%, and 7.6% among SSc patients with ILD. CPFE-SSc patients were more likely to be male (75 % vs 18%, p < 0.0001), smokers (83 % vs 33%, p < 0.0001), and to have limited cutaneous SSc (53 % vs 24% p < 0.01) than ILD-SSc controls. No specific autoantibody was significantly associated with CPFE. At diagnosis, CPFE-SSc patients had a greater decrease in carbon monoxide diffusing capacity (DLCO 39 ± 13 % vs 51 ± 12% of predicted value, p < 0.0001) when compared to SSc-ILD controls, whereas lung volumes (total lung capacity and forced vital capacity) were similar. During follow-up, CPFE-SSc patients more frequently developed precapillary pulmonary hypertension (PH) (44 % vs 11%, p < 10−4), experienced more frequent unscheduled hospitalizations (50 % vs 25%, p < 0.01), and had decreased survival (p < 0.02 by Kaplan–Meier survival analysis) as compared to ILD-SSc controls. The CPFE syndrome is a distinct pulmonary manifestation in SSc, with higher morbidity and mortality. Early diagnosis of CPFE by chest CT in SSc patients (especially smokers) may result in earlier smoking cessation, screening for PH, and appropriate management. [ABSTRACT FROM AUTHOR]

Background and objective: Combined pulmonary fibrosis and emphysema (CPFE) is characterized by preserved lung volume and slower lung function decline. However, it is unclear at what extent emphysema begins to impact respiratory physiology and prognostic characteristics in idiopathic pulmonary fibrosis (IPF). We estimated the extent of emphysema that could be used to define CPFE in IPF. Methods: The extent of emphysema was observed on high‐resolution computed tomography scans and measured by a texture‐based automated quantification system in 209 IPF patients. We analysed the impact of differences in the extent of emphysema on the annual decline rate and prognostic significance of lung function parameters. Results: The extent of emphysema was ≥5% in 53 patients (25%), ≥10% in 23 patients (11%) and ≥15% in 12 patients (6%). Patients with emphysema to an extent of ≥5% were more frequently men and ever‐smokers; they had more preserved lung volume and lower forced vital capacity (FVC) decline rates than those with no or trivial emphysema. The FVC decline rate was a significant predictor of mortality in patients with no or trivial emphysema (hazard ratio (HR): 0.933, P < 0.001) and in patients with an extent of emphysema ≥5% (HR: 0.906, P < 0.001). However, diffusing capacity of the lung for carbon monoxide (DLCO) was the most significant prognostic factor in those patients with an extent of emphysema ≥10% (HR: 0.972, P = 0.040) and ≥15% (HR: 0.942, P = 0.023). A 10% cut‐off value for the extent of emphysema created the most significant difference in the annual FVC decline rate in IPF patients. Conclusion: In IPF, emphysema to an extent of ≥10% affects both the annual decline rate and the prognostic significance of FVC. This extent could be used to define CPFE. Patients with idiopathic pulmonary fibrosis (IPF) and emphysema exceeding 10% had more preserved lung volume and lower rates of decline in forced vital capacity (FVC) than those with no or trivial emphysema. Diffusing capacity of the lung for carbon monoxide (DLCO) was the most significant prognostic factor in these patients. See relatedEditorial [ABSTRACT FROM AUTHOR]

Atsushi Hata,1,2 Yasuo Sekine,1 Ohashi Kota,1 Eitetsu Koh,1 Ichiro Yoshino2 1Department of Thoracic Surgery, Tokyo Women’s Medical University Yachiyo Medical Centre, Yachiyo, 2Department of General Thoracic Surgery, Graduate School of Medicine, Chiba University, Chiba City, Chiba, Japan Purpose: The outcome of radical surgery for lung cancer was investigated in patients with combined pulmonary fibrosis and emphysema (CPFE). Methods: A retrospective chart review involved 250 patients with lung cancer who underwent pulmonary resection at Tokyo Women’s Medical University Yachiyo Medical Center between 2008 and 2012. Based on the status of nontumor-bearing lung evaluated by preoperative computed tomography (CT), the patients were divided into normal, emphysema, interstitial pneumonia (IP), and CPFE groups, and their clinical characteristics and surgical outcome were analyzed. Results: The normal, emphysema, IP, and CPFE groups comprised 124 (49.6%), 108 (43.2%), seven (2.8%), and eleven (4.4%) patients, respectively. The 5-year survival rate of the CPFE group (18.7%) was significantly lower than that of the normal (77.5%) and emphysema groups (67.1%) (P

Abstract Myeloperoxidase antineutrophil cytoplasmic autoantibody (MPO-ANCA) is well-known as a serological marker for small-vessel vasculitis. However, when a smoker with interstitial lung disease (ILD) exhibits serum ANCA positivity without systemic vasculitis, diagnosis is a matter of debate; the relationship between smoking and ANCA is unknown. We report a case of combined pulmonary fibrosis and emphysema (CPFE) with elevated MPO-ANCA. Surgical lung biopsy showed emphysema and fibrotic interstitial pneumonia without vasculitis. The MPO-ANCA level decreased after smoking cessation, and no vasculitis or progression was observed during 3 years of follow-up. This suggested that smoking cessation was related to normalization of MPO-ANCA and corresponding disease activity. [ABSTRACT FROM AUTHOR]

Purpose: We evaluated the long-term outcomes of clinical stage IA non-small cell lung cancer (NSCLC) patients with combined pulmonary fibrosis and emphysema (CPFE) who underwent lobectomy. Methods: We reviewed the chest computed tomography (CT) findings and divided the patients into normal, fibrosis, emphysema and CPFE groups. We evaluated the relationships among the CT findings, the clinicopathological findings and postoperative survival. Results: The patients were classified into the following groups based on the preoperative chest CT findings: normal lung, n = 187; emphysema, n = 62; fibrosis, n = 8; and CPFE, n = 17. The patients with CPFE were significantly older, more likely to be men and smokers, had a higher KL-6 level and lower FEV 1.0% value and had a higher rate of squamous cell carcinoma. The 5-year overall survival (OS) and disease-free survival rates were as follows: normal group, 82.5 and 76.8%; emphysema group, 80.0 and 74.9%; fibrosis group, 46.9 and 50%; and CPFE group, 36.9 and 27.9%, respectively ( p < 0.01). A univariate and multivariate analysis determined that the pathological stage and CT findings were associated with OS. Conclusions: CPFE is a significantly unfavorable prognostic factor after lobectomy, even in early-stage NSCLC patients with a preserved lung function. [ABSTRACT FROM AUTHOR]

Background: It remains unclear whether the preoperative pulmonary function parameters and prognostic indices that are indicative of nutritional and immunological status are associated with prognosis in lung cancer patients with combined pulmonary fibrosis and emphysema (CPFE) who have undergone surgery. Objective: The aim of this study is to identify prognostic determinants in these patients. Methods: The medical records of all patients with lung cancer associated with CPFE who had undergone surgery at Shinshu University Hospital were retrospectively reviewed to obtain clinical data, including the results of preoperative pulmonary function tests and laboratory examinations, chest highresolution computed tomography (HRCT), and survival. Results: Univariate Cox proportional hazards regression analysis showed that a high pathological stage of the lung cancer, a higher preoperative serum carcinoembryonic antigen level, and a higher preoperative composite physiologic index (CPI) were associated with a high risk of death. Multivariate analysis showed that a high pathological stage of the lung cancer (HR: 1.579; p = 0.0305) and a higher preoperative CPI (HR: 1.034; p = 0.0174) were independently associated with a high risk of death. In contrast, the severity of fibrosis or emphysema on chest HRCT, the individual pulmonary function parameters, the prognostic nutritional index, the neutrophil-to-lymphocyte ratio, and the platelet-to-lymphocyte ratio were not associated with prognosis. In the Kaplan-Meier analysis, the log-rank test showed significant differences in survival between the high-CPI and the low-CPI group (p = 0.0234). Conclusion: The preoperative CPI may predict mortality and provide more powerful prognostic information than individual pulmonary function parameters in lung cancer patients with CPFE who have undergone surgery. [ABSTRACT FROM AUTHOR]

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Aims To evaluate pulmonary vasculopathy in an autopsy series of patients with combined pulmonary fibrosis and emphysema ( CPFE), and compare these findings with those of patients with idiopathic pulmonary fibrosis ( IPF) alone and emphysema alone. Methods and results We retrospectively analysed the clinical, radiological and pathological features of 26 patients with CPFE, 11 with IPF, and 23 with emphysema. We evaluated pulmonary vascular, venous-venular and arteriolar tissue changes in the fibrotic, emphysematous and relatively unaffected (preserved) areas by using the Heath-Edwards scoring system. We found moderate-to-severe vasculopathy in the CPFE group, but no significant differences in the fibrotic and emphysematous areas among the three groups. However, in the preserved area, the grading was significantly different among the three groups ( P < 0.001), and vasculopathy in the CPFE group was the most severe. Although venous-venular and arteriolar changes in almost all fibrotic and emphysematous areas in the three groups showed no significant differences, there were significant differences in venous-venular ( P = 0.004) and arteriolar ( P < 0.001) changes in the preserved area among the three groups, which were most prevalent in the CPFE group. In the CPFE group, venous-venular changes and vasculopathy by Heath-Edwards grading were highest in the fibrotic area and lowest in the preserved area. Conclusions These results imply that pulmonary vasculopathy in patients with CPFE could occur in the whole lung tissue. This may explain the tendency for it to lead to the development of pulmonary hypertension in CPFE cases. [ABSTRACT FROM AUTHOR]

Combined pulmonary fibrosis and emphysema (CPFE) is an “umbrella term” encompassing emphysema and pulmonary fibrosis, but its pathogenesis is not known. We established two models of CPFE in mice using tracheal instillation with bleomycin (BLM) or murine gammaherpesvirus 68 (MHV-68). Experimental mice were divided randomly into four groups: A (normal control, n = 6), B (emphysema, n = 6), C (emphysema + MHV-68, n = 24), D (emphysema + BLM, n = 6). Group C was subdivided into four groups: C1 (sacrificed on day 367, 7 days after tracheal instillation of MHV-68); C2 (day 374; 14 days); C3 (day 381; 21 days); C4 (day 388; 28 days). Conspicuous emphysema and interstitial fibrosis were observed in BLM and MHV-68 CPFE mouse models. However, BLM induced diffuse pulmonary interstitial fibrosis with severely diffuse pulmonary inflammation; MHV-68 induced relatively modest inflammation and fibrosis, and the inflammation and fibrosis were not diffuse, but instead around bronchioles. Inflammation and fibrosis were detectable in the day-7 subgroup and reached a peak in the day-28 subgroup in the emphysema + MHV-68 group. Levels of macrophage chemoattractant protein-1, macrophage inflammatory protein-1α, interleukin-13, and transforming growth factor-β1 in bronchoalveolar lavage fluid were increased significantly in both models. Percentage of apoptotic type-2 lung epithelial cells was significantly higher; however, all four types of cytokine and number of macrophages were significantly lower in the emphysema + MHV-68 group compared with the emphysema  + BLM group. The different changes in pathology between BLM and MHV-68 mice models demonstrated different pathology subtypes of CPFE: macrophage infiltration and apoptosis of type-II lung epithelial cells increased with increasing pathology score for pulmonary fibrosis. [ABSTRACT FROM AUTHOR]

Several groups have described a syndrome in which idiopathic pulmonary fibrosis (IPF) coexists with pulmonary emphysema. This comes as no surprise since both diseases are associated with a history of exposure to cigarette smoke. The syndrome of combined pulmonary fibrosis and emphysema (CPFE) is characterised by upper lobe emphysema and lower lobe fibrosis. Physiological testing of these patients reveals preserved lung volume indices contrasted by markedly impaired diffusion capacity. The incidence of CPFE remains unknown but several case series suggest that this subgroup may comprise up to 35% of patients with IPF. CPFE is a strong determinant of associated pulmonary hypertension (PH). In addition, CPFE has major effects on measures of physiological function, exercise capacity and prognosis, and may affect the results of pulmonary fibrosis trials. Further studies are needed to ascertain the aetiology, morbidity, mortality and management of the CPFE syndrome, with or without PH, and to evaluate novel therapeutic options in CPFE.

In 2015, the international guidelines for diagnosis and treatment of pulmonary hypertension were updated. Group 3 of the current classification includes pulmonary hypertension associated with chronic obstructive pulmonary disease (COPD), interstitial lung disease, other pulmonary diseases with restrictive and obstructive pattern, sleep-disordered breathing, alveolar hypoventilation disorders, chronic exposure to high altitude, and developmental lung diseases. Pulmonary hypertension associated with COPD and interstitial lung disease is common but difficult to manage, as no long-term randomised controlled trial has been conducted with specific pulmonary arterial hypertension drugs in pulmonary hypertension associated with COPD, and the one recent RCT in pulmonary hypertension associated with interstitial lung disease had to be stopped early due to a possible increased risk of death and side effects in the treatment group. Specific treatment may thus be harmful and may worsen gas exchange as a result of possible recruitment of less oxygenised areas, i.e. by increasing ventilation-perfusion mismatch. Management of pulmonary hypertension patients with chronic lung diseases requires careful evaluation and understanding of pathophysiological mechanisms. Interestingly, mediators in PAH and in fibrotic lung disease show some overlaps. Several drugs effective in pulmonary arterial hypertensio have been evaluated for anti-fibrotic treatment in interstitial lung disease, but until today without consistent success. While new drugs with anti-fibrotic effects are now accessible, a specific evidence-based treatment for pulmonary hypertension in interstitial lung disease or COPD with or without emphysema is not yet available.