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Background In non-small cell lung cancer (NSCLC) patients, concomitant idiopathic pulmonary fibrosis (IPF) and emphysema (CPFE) are independently related to poor survival. CPFE is a condition with features of both pulmonary fibrosis and emphysema. Here, we evaluated the effect of CPFE and IPF alone on the outcomes of NSCLC patients. Patients and methods We retrospectively evaluated 283 patients with CPFE or IPF who were diagnosed with NSCLC between November 2003 and February 2018 at two tertiary care hospitals in South Korea. Patients were classified into CPFE and IPF groups according to chest computed tomography findings. Results One-hundred-and-seven patients (37.8%; mean age: 70.1 years; men 97.2%) had CPFE. Compared with IPF patients, CPFE patients had a heavier smoking history; lower diffusing capacity of carbon monoxide (78.0% vs 64.8%, p P = 0.029) was significantly correlated with acute exacerbations (AEs). In a Cox proportional hazards analysis, stage > III NSCLC, higher Eastern Cooperative Oncology Group performance status, and higher gender–age–physiology index score was related to higher mortality. However, CPFE was not related to a higher mortality rate in univariate (hazard ratio [HR]: 1.00; 95% CI: 0.75–1.32, P = 0.972) or multivariate analysis (HR: 0.89; 95% CI: 0.66–1.21, P = 0.466). Conclusions AE risk, but not all-cause mortality, was higher in patients with CPFE and NSCLC than in those with IPF and NSCLC. Physicians should be aware of the exaggerated risk of AE in patients with concomitant CPFE and NSCLC.

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 (DLCO). 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.

International audience; Background: 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).Methods: 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.Results: 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.Conclusions: The CPFE syndrome is a distinct pulmonary manifestation in SSc, with higher morbidity and mortality. Early diagnosis of CPFE by chest CF in SSc patients (especially smokers) may result in earlier smoking cessation, screening for PH, and appropriate management.

Cigarettes are well-recognized risk factors responsible for the emergence of a variety of pathologic conditions affecting both the airways and the lungs. Smoking-related lung diseases can be classified as chronic obstructive pulmonary disease (COPD) and several types of interstitial diseases, such as pulmonary Langerhans cell histiocytosis, bronchiolitis, desquamative interstitial pneumonitis, acute eosinophilic pneumonia, and interstitial fibrosing lung diseases. The evidence of combined lower lung fibrosis and predominant upper lung emphysema is renowned as a distinct clinical entity, named combined pulmonary fibrosis and emphysema. Although computerized tomography permits an adequate classification and distinction of these diseases, the clinical, imaging, and histological features often overlap and coexist in a single patient. Therefore, a combined radiologic and pathologic approach, in the appropriate clinical setting, is useful for best comprehension and distinction of these entities. Our goals are to describe the imaging features in smoking-related lung diseases and how the pathological manifestations translate on high-resolution computerized tomography.

Combined pulmonary fibrosis and emphysema (CPFE) is a syndrome that predominantly affects male smokers or ex-smokers and it has a mortality rate of 55% and a median survival of 5 years. Pulmonary hypertension (PH) is a frequently fatal complication of CPFE. Despite this dismal prognosis, no curative therapies exist for patients with CPFE outside of lung transplantation and no therapies are recommended to treat PH. This highlights the need to develop novel treatment approaches for CPFE. Studies from our group have demonstrated that both adenosine and its receptor ADORA2B are elevated in chronic lung diseases. Activation of ADORA2B leads to elevated levels of hyaluronan synthases (HAS) and increased hyaluronan, a glycosaminoglycan that contributes to chronic lung injury. We hypothesize that ADORA2B and hyaluronan contribute to CPFE. Using isolated CPFE lung tissue, we characterized expression levels of ADORA2B and HAS. Next, using a unique mouse model of experimental lung injury that replicates features of CPFE, namely airspace enlargement, PH and fibrotic deposition, we investigated whether 4MU, a HAS inhibitor, was able to inhibit features of CPFE. Increased protein levels of ADORA2B and HAS3 were detected in CPFE and in our experimental model of CPFE. Treatment with 4MU was able to attenuate PH and fibrosis but not airspace enlargement. This was accompanied by a reduction of HAS3-positive macrophages. We have generated pre-clinical data demonstrating the capacity of 4MU, an FDA-approved drug, to attenuate features of CPFE in an experimental model of chronic lung injury. This article has an associated First Person interview with the first author of the paper., Summary: Fibrotic deposition and PH are inhibited by the FDA-approved drug hymecromone, suggesting hyaluronan synthesis inhibition as a potential therapy for CPFE and highlighting a novel mechanism through HAS3-positive macrophages.

Background Fenestration is performed in patients with bronchopleural fistula to avoid a life-threatening situation. However, usually, this procedure is required 9-cm mean length of the incision with rib resection. Case presentation A 73-year-old man underwent right lower lobectomy with lymph node dissection (ND2a-2) for primary lung cancer (cT1cN2M0 Stage IIIA) with combined pulmonary fibrosis and emphysema. He developed a bronchopleural fistula on postoperative day 20, and we performed emergency fenestration without rib resection using a Lap-protector. The patient reported minimal pain postoperatively. As the rapid deterioration of the general condition due to the recurrence of the tumor was observed at the time of his 1-year postoperative follow-up, closing of the thoracic cavity was abandoned. However, using this fenestration, the control of infection in the thoracic cavity could be sufficiently performed without complications such as pain and pneumonia, and his routine activities were unaffected postoperatively. Conclusion Compared with conventional method, fenestration without rib resection using a Lap-protector is a more convenient and painless technique for postoperative bronchopleural fistula.

Background Tobacco smoking causes a variety of smoking-related diseases, death, and economic damage. Despite targeted anti-smoking campaigns, tobacco-related deaths are expected to increase in Japan. We investigated the current state of non-cancerous lung diseases such as idiopathic interstitial pneumonias (IIPs), chronic obstructive pulmonary disease (COPD), and combined pulmonary fibrosis and emphysema (CPFE), which are known to be highly related to tobacco smoking. Methods This prospective multi-institutional observational study involved 29 major hospitals within the Fukuoka Prefecture area (Fukuoka tobacco-related lung disease registry study group). Patients diagnosed with IIPs, including CPFE and COPD, registered from September 1, 2013 to April 30, 2016 were included. Clinical background information, laboratory and pulmonary function test results, findings of imaging tests, including chest radiography and chest computed tomography, and DNA isolated from peripheral blood were collected from each patient. Follow-up surveillance involved collection of data regarding the exacerbation of disease and death until 5 years of registration. In the present study, we report the baseline characteristics of the patients registered in this surveillance study. Results Overall, 1016 patients (524 with IIPs, including 145 CPFE and 492 with COPD) were enrolled. Among the patients with COPD, 96.8% were current or former smokers. Among the patients with IIPs, 69.9% were current or former smokers. Conclusion This study revealed the current status of lung diseases potentially related to tobacco smoking in Fukuoka Prefecture. Both COPD and CPFE were highly related to tobacco smoking, whereas 30% of patients with IIPs had never smoked.

Background: Combined pulmonary fibrosis and emphysema (CPFE) is frequently associated with lung cancer. However, the impact and outcomes of lung cancer in patients with CPFE are unclear. Objective: We investigated the impact of lung cancer in patients with CPFE in terms of acute exacerbation (AE) and mortality, and identified the mortality predictors of patients with CPFE and lung cancer. Methods: We retrospectively reviewed 12-year medical records of patients at the Korea University Guro Hospital. Based on computed tomography findings, we selected CPFE patients with and without lung cancer, and analyzed age, sex, smoking status and history, body mass index, past medical history, pulmonary function, the gender, age, and physiology (GAP) score, AE, and mortality. Results: Of 227 CPFE patients, 61 were diagnosed with lung cancer. While 10 of the 61 patients experienced AE, 41 died during the observation period. Lung cancer was a significant predictor of AE (hazard ratio [HR] 3.27, 95% confidence interval [CI ]1.44–7.43, P

Combined pulmonary fibrosis and emphysema (CPFE) is a common but under-recognized syndrome characterized with distinct profiles of both pulmonary fibrosis and emphysema. Pulmonary hypertension (PH) is particularly prone to develop as a common complication, leading to exercise limitation and worse prognosis of CPFE. Although the therapy of patients with PH from CPFE cannot be endorsed, an individual treatment may be considerable when accompanying severe PH. We report a case of a 71-year-old male with PH from CPFE, who improved pulmonary arterial compliance (PAC) and exercise capacity in response to pulmonary vasodilator. Keywords: Combined pulmonary fibrosis and emphysema, Pulmonary hypertension, Pulmonary arterial compliance, Pulmonary vasodilator

ObjectivesThis multicentre study aimed to investigate the overall mortality of combined pulmonary fibrosis and emphysema (CPFE) in systemic sclerosis (SSc) and to compare CPFE-SSc characteristics with those of other SSc subtypes (with interstitial lung disease—ILD, emphysema or neither).MethodsChest CTs, anamnestic data, immunological profile and pulmonary function tests of patients with SSc were retrospectively collected. Each chest CT underwent a semiquantitative assessment blindly performed by three radiologists. Patients were clustered in four groups: SSc-CPFE, SSc-ILD, SSc-emphysema and other-SSc (without ILD nor emphysema). The overall mortality of these groups was calculated by Kaplan-Meier method and compared with the stratified log-rank test; Kruskal-Wallis test, t-Student test and χ² test assessed the differences between groups. PResultsWe enrolled 470 patients (1959 patient-year); 15.5 % (73/470) died during the follow-up. Compared with the SSc-ILD and other-SSc, in SSc-CPFE there was a higher prevalence of males, lower anticentromere antibodies prevalence and a more reduced pulmonary function (pConclusionsCPFE increases the mortality risk in SSc along with a highly impaired lung function. These findings strengthen the importance to take into account emphysema in patients with SSc with ILD.

Systemic sclerosis (SSc) is a multi-systemic autoimmune disease that mainly affects the skin, lungs, gastrointestinal tract, heart and kidneys. Pulmonary disease in patients with SSc is strongly associated with mortality. The mechanisms involved into its pathophysiology include the activation of autoimmune cells and hyperplasia of fibroblasts with an increased capacity to produce collagen and diminished collagen breakdown. Although pulmonary biopsy is the gold standard for the diagnosis of interstitial lung disease in SSc, the most commonly used method is high-resolution computed tomography due to its high sensitivity and specificity. Herein, a comprehensive review on the pulmonary involvement in SSc is presented highlighting the radiologic–pathologic correlations. © 2016 Elsevier B.V.

Combined pulmonary fibrosis and emphysema (CPFE) is an important risk factor for lung cancer (LC), because most patients with CPFE are smokers. However, the histological characteristics of LC in patients with CPFE (LC‐CPFE) remain unclear. We conducted this study to explore the clinicopathological characteristics of LC‐CPFE. We retrospectively reviewed data from 985 patients who underwent resection for primary LC, and compared the clinicopathological characteristics of patients with LC‐CPFE and non‐CPFE LC. We identified 72 cases of LC‐CPFE, which were significantly associated with squamous cell carcinoma (SqCC) histology (n = 46, P

Background There is only limited information on the clinical impact of combined pulmonary fibrosis and emphysema (CPFE) on postoperative and survival outcomes among patients with resected lung cancer. Methods In a retrospective analysis, data were reviewed from 685 patients with resected lung cancer between 2006 and 2011. The clinical impact of thin-section computed tomography (TSCT)–determined emphysema, fibrosis, and CPFE on postoperative and survival outcomes was evaluated. Results The emphysema group comprised 32.4% of the study population, the fibrosis group 2.8%, and the CPFE group 8.3%. The CPFE group had a more advanced pathologic stage and higher prevalence of squamous cell carcinoma as compared with the normal group without emphysema or fibrosis findings on TSCT. The incidence of postoperative complications was significantly higher in the CPFE group. Overall, the 30-day mortality in the CPFE group was 5.3%. Cancer recurrence at pathologic stage I and death due to either cancer or other causes were significantly higher in the CPFE group. Survival curves indicated that a finding of CPFE was associated with worse overall survival for patients with any stage disease. Multivariate analysis suggested that pathologic stage and CPFE were independent factors associated with worse overall survival. The adjusted hazard ratio of overall survival for the CPFE group versus the normal group was 2.990 (95% confidence interval: 1.801 to 4.962). Conclusions Among patients with resected lung cancer, the presence of TSCT-determined CPFE might predict worse postoperative and survival outcomes.

Combined pulmonary fibrosis and emphysema (CPFE) is a clinical entity characterized by the coexistence of upper lobe emphysema and lower lobe fibrosis. Patients with this condition experience severe dyspnea and impaired gas exchange with preserved lung volumes. The diagnosis of the CPFE syndrome is based on HRCT imaging, showing the coexistence of emphysema and pulmonary fibrosis both in varying extent and locations within the lung parenchyma. Individual genetic background seem to predispose to the development of the disease. The risk of the development of pulmonary hypertension in patients with CPFE is high and related to poor prognosis. CPFE patients also present a high risk of lung cancer. Mortality is significant in patients with CPFE and median survival is reported between 2.1 and 8.5 years. Currently, no specific recommendations are available regarding the management of patients with CPFE. In this review we provide information on the existing knowledge on CPFE regarding the pathophysiology, clinical manifestations, imaging, complications, possible therapeutic interventions and prognosis of the disease.

Pneumomediastinum is an uncommon condition which is defined by the presence of air in the mediastinum. It may result from a number of causes, but at times the underlying aetiology remains obscure. The present study aims to review the clinical and imaging features in patients who presented with pneumomediastinum alone or in association with other findings in order to establish the aetiological diagnosis. We report here, a series of cases with pneumomediastinum of various unusual aetiologies and also the clinical profile, predisposing factors and outcome of these patients along with the associated complications. METHODS We retrospectively reviewed the records of all patients who presented to the respiratory unit of our hospital with the diagnosis of pneumomediastinum over a period of 2 years from 2013-2015. The cases of pneumomediastinum resulting from trauma and iatrogenic causes were excluded from the study. RESULTS A total of six patients (4 males and 2 females) with pneumomediastinum were identified during the study period after applying the exclusion criteria. The most common presenting symptom in these cases was shortness of breath followed by dry cough, chest pain and fever. Subcutaneous emphysema and Hamman sign was identified in one patient each. Of the six cases, preexisting lung disease was identified in 3 patients and these included connective tissue disease related interstitial lung disease in two cases and combined pulmonary fibrosis and emphysema in one case. In the remaining three cases, the causes of pneumomediastinum were Pneumocystis carinii pneumonia (PCP) in HIV positive patient, pulmonary tuberculosis in another and spontaneous oesophageal perforation in the third. Coexisting pneumothorax was present in 3 out of 6 cases. The mean duration of hospital stay in these six patients was 8 days. No recurrence of pneumomediastinum was seen in any of the six patients during six months of followup. CONCLUSIONS Pneumomediastinum is a condition with diverse aetiologies. It is important to identify the underlying cause of pneumomediastinum in order to manage these patients. Spontaneous pneumomediastinum needs to be differentiated from secondary pneumomediastinum as the latter is a more morbid condition and has to be managed promptly in order to avoid unfavourable outcome.

Resume Introduction Le syndrome d’emphyseme des sommets et fibrose pulmonaire des bases combines (SEF) est une entite rare survenant le plus souvent dans un contexte de tabagisme et/ou de connectivites. En revanche, l’association avec les vascularites demeure encore anecdotique. Observation Il est rapporte le cas d’un SEF chez un homme âge de 44 ans, petit fumeur et sans autre antecedent significatif. Le patient se presentait pour fievre, toux trainante avec dyspnee d’effort aboutissant progressivement a un tableau d’insuffisance respiratoire aigue. La tomodensitometrie thoracique montrait l’association d’un emphyseme avec des opacites pulmonaires en verre depoli bilaterales. Trois ans apres, se developpaient une fibrose pulmonaire en rayon de miel avec une micropolyangeite se manifestant par une glomerulonephrite extra-capillaire et justifiant l’instauration d’un traitement immunosuppresseur associe a une corticotherapie systemique. Apres une periode de stabilisation de 6 annees, le patient a developpe une insuffisance respiratoire chronique avec hypertension pulmonaire moderee imposant une oxygenotherapie de longue duree avec une ventilation non invasive a domicile. Conclusion Ce type d’association suggere que les maladies auto-immunes, dont la micropolyangeite, pourraient jouer un role pathogenique commun dans le developpement des lesions du SEF.

There is increased awareness of smoking-related lung diseases other than lung cancer and chronic obstructive pulmonary disease. Concurrently, there is general acceptance that there is difficulty in establishing a specific diagnosis of smoking-related interstitial lung disease (ILD), as many patients may not undergo biopsy to facilitate a specific histopathologic diagnosis. Cases that do proceed to biopsy may demonstrate multiple abnormalities, and histologic overlap between different disease processes may confound the picture. This review outlines the key aspects of smoking-related lung disease, including entities secondary to smoking-related lung inflammation such as respiratory bronchiolitis-ILD, desquamative idiopathic pneumonia, and pulmonary Langerhans cell histiocytosis, as well as chronic fibrosing lung diseases strongly associated with cigarette smoke including idiopathic pulmonary fibrosis, combined pulmonary fibrosis and emphysema, nonspecific interstitial pneumonia, and rheumatoid arthritis-ILD. The focus will be on incorporation of clinical findings, key pulmonary function testing parameters, high-resolution computer tomography (HRCT) findings, and pathologic correlates in refining the differential diagnosis and differentiating between the various entities.

Combined pulmonary fibrosis and emphysema is a relatively newly defined entity, which has been deeply studied in the recent years. Despite the wide numbers of papers on this topic, there are still several open questions about pathogenesis, epidemiology, natural history and prognosis. The diagnosis could be assessed only after HRCT scan as functional tests often result in an underestimation of this syndrome. What radiologists need to know about this syndrome consists in the heterogeneity of appearances: emphysema is mainly paraseptal and fibrotic pattern could be variable, including the variant of airspace enlargement with fibrosis which needs to be differentiated from honeycombing. A special attention must be paid on complications which could worsen the prognosis, such as pulmonary hypertension and lung cancer. Further studies are needed to address if the type of fibrotic pattern as well as fibrosis CT index could be considered as prognostic factors. Thus, the role of radiologists in the management of these patients is crucial as it involves diagnosis, detection of complications and could possible concerns the identification of patients at higher risk.

Objective Since the term "combined pulmonary fibrosis and emphysema" (CPFE) was first proposed, the co-existence of pulmonary fibrosis and pulmonary emphysema (PE) has drawn considerable attention. However, conflicting results on the clinical characteristics of patients with both pulmonary fibrosis and PE have been published because of the lack of an exact definition of CPFE. The goal of this study was thus to clarify the clinical characteristics and phenotypes of idiopathic interstitial pneumonia (IIP) with PE. Methods We retrospectively analyzed IIP patients who had been admitted to our hospital. Their chest high-resolution computed tomography images were classified into two groups according to the presence of PE. We then performed a cluster analysis to identify the phenotypes of IIP patients with PE. Results Forty-four (53.7%) out of 82 patients had at least mild emphysema in their bilateral lungs. The cluster analysis separated the IIP patients with PE into three clusters. The overall survival rate of one cluster that consisted of mainly idiopathic pulmonary fibrosis (IPF) patients was significantly worse than those of the other clusters. Conclusion Three different phenotypes can be identified in IIP patients with PE, and IPF with PE is a distinct clinical phenotype with a poor prognosis.

Objectives Combined pulmonary fibrosis and emphysema (CPFE) is a unique disorder. The aim of this study was to compare the surgical outcomes of lung cancer patients with CPFE and those with idiopathic pulmonary fibrosis (IPF) without emphysema. Methods A total of 1548 patients who underwent surgery for primary lung cancer between January 2001 and December 2012 were retrospectively reviewed. Results Of the 1548 patients, 55 (3.6%) had CPFE on computed tomography (CT), and 45 (2.9%) had IPF without emphysema. The overall and disease-free 5-year survival rates for patients with CPFE were not significantly worse than those for patients with IPF without emphysema (24.9% vs. 36.8%, p = 0.814; 39.8% vs. 39.3%, p = 0.653, respectively). Overall, 21 (38.1%) patients with CPFE and nine patients (20.0%) with IPF without emphysema developed postoperative cardiopulmonary complications. Patients with CPFE had significantly more postoperative cardiopulmonary complications involving pulmonary air leakage for >6 days, hypoxemia, and arrhythmia than patients with IPF without emphysema (p = 0.048). Conclusions There was no significant difference in survival after surgical treatment between CPFE patients and IPF patients without emphysema, but CPFE patients had significantly higher morbidity than IPF patients without emphysema.

Combined idiopathic pulmonary fibrosis with pulmonary emphysema (CPFE) is a syndrome with a characteristic presentation of upper lobe emphysema and lower lobe fibrosis. Dyspnea on exertion (DOE) is a major symptom of CPFE. We report a patient with DOE due to CPFE who was successfully treated with acupuncture.Case report.A 72-year-old Japanese man with a 4-year history of DOE was diagnosed with CPFE 2 years previously in another hospital. He received standard Western medicine treatment, which included bronchodilators. However, his DOE did not improve. Consequently, he visited our hospital for acupuncture treatment and received acupuncture treatment once a week for 1 year.After 10 weeks of acupuncture treatment, the results of the 6-minute walk test (6-minute walking distance, 379 m; lowest oxygen saturation, 86%; modified Borg dyspnea scale score: 2 units) were better than those at baseline (352 m, 84%, 4 units, respectively). These values were sustained at both 30 weeks (470 m, 88%, 1 unit) and 60 weeks (473 m, 85%, 2 units). Serum interstitial biomarkers, Krebs von den Lungen and surfactant protein-D, decreased after commencement of acupuncture therapy.A patient with CPFE showed improvements in dyspnea scores, exercise tolerance, and serum biomarkers during a 1-year course of acupuncture treatment. Use of acupuncture might be an effective adjunct therapy in relieving DOE due to CPFE. A large, well-designed cohort study that includes patients with CPFE treated with acupuncture should be conducted.

In patients with chronic fibrosing interstitial lung disease (ILD), a progressive fibrosing phenotype (PF-ILD) may develop, but information on the frequency and characteristics of this population outside clinical trials is lacking. We assessed the characteristics and outcomes of patients with PF-ILD other than idiopathic pulmonary fibrosis (IPF) in a real-world, single-centre clinical cohort. The files of all consecutive adult patients with fibrosing ILD (2010–2017) were examined retrospectively for pre-defined criteria of ≥10% fibrosis on high-resolution computed tomography and progressive disease during overlapping windows of 2 years. Baseline was defined as the date disease progression was identified. Patients receiving nintedanib or pirfenidone were censored from survival and progression analyses. In total, 1395 patients were screened; 617 had ILD other than IPF or combined pulmonary fibrosis and emphysema, and 168 had progressive fibrosing phenotypes. In 165 evaluable patients, median age was 61 years; 57% were female. Baseline mean forced vital capacity (FVC) was 74±22% predicted. Median duration of follow-up was 46.2 months. Annualised FVC decline during the first year was estimated at 136±328 mL using a linear mixed model. Overall survival was 83% at 3 years and 72% at 5 years. Using multivariate Cox regression analysis, mortality was significantly associated with relative FVC decline ≥10% in the previous 24 months (p, In a real-world clinical cohort (PROGRESS), progressive fibrosing interstitial lung disease was characterised by continued lung function decline. Lung function decline, age and underlying diagnosis subgroup predicted mortality. https://bit.ly/2EB3OpF

Background:Interstitial lung disease (ILD) represents a frequent extra-glandular manifestation of primary Sjögren’s Syndrome (pSS). Limited published data regarding phenotyping and treatment exists. Advances in managing specific ILD phenotypes have not been comprehensively explored in patients with coexisting pSS.Objectives:This retrospective study aimed to phenotype lung diseases occurring in a well-described pSS cohort and describe treatment course and outcomes.Methods:Between April 2018 and September 2019, all pSS patients attending our Outpatient clinic were screened for possible lung involvement. Clinical, laboratory and computer tomography (CT) findings were analysed. Patients were classified according to CT findings into 5 groups: usual interstitial pneumonia (UIP), non-specific interstitial pneumonia (NSIP), desquamative interstitial pneumonia (DIP), combined pulmonary fibrosis and emphysema (CPFE) and unspecific-ILD.Results:Lung involvement was confirmed in 24/240 patients (10%). Clinically manifest pSS occurred later in patients with ILD vs. non-ILD (53.2 [42.0-61.7]vs.62.3 [55.6-68.8] years; p=0.0016). The commonest phenotype was UIP n=10 (41%), followed by NSIP n=7 (29%), DIP n=2 (8%), CPFE n=2 (8%) and unspecific-ILD n=3 (13%). Forced vital capacity (FVC) and carbon monoxide diffusion capacity (DLCO) appeared lower in UIP and DIP, without reaching a significant difference. Treatment focused universally on intensified immunosuppression, with 12/24 patients (50%) receiving cyclophosphamide. No anti-fibrotic treatments were used. Follow-up was median 13.2 [7.9-72.3] months, during which 6/24 (25%) patients exhibited a further decline in FVC. No deaths occurred.Conclusion:Lung involvement in pSS is heterogeneous. Better phenotyping and tailored treatment may improve outcomes and requires further evaluation in larger prospective studies.Disclosure of Interests:None declared

Prolidase deficiency is a new genetic cause of combined pulmonary fibrosis and emphysema syndrome in the adulthttp://bit.ly/2QRgqMH

Background: The aetiology and inflammatory profile of combined pulmonary fibrosis and emphysema (CPFE) remain uncertain currently. Objective: We aimed to examine the levels of inflammatory proteins in lung tissue in a cohort of patients with emphysema, interstitial pulmonary fibrosis (IPF), and CPFE. Materials and methods: Explanted lungs were obtained from subjects with emphysema, IPF, CPFE, (or normal subjects), and tissue extracts were prepared. Thirty-four inflammatory proteins were measured in each tissue section. Results: The levels of all 34 proteins were virtually indistinguishable in IPF compared with CPFE tissues, and collectively, the inflammatory profile in the emphysematous tissues were distinct from IPF and CPFE. Moreover, inflammatory protein levels were independent of the severity of the level of diseased tissue. Conclusions: We find that emphysematous lung tissues have a distinct inflammatory profile compared with either IPF or CPFE. However, the inflammatory profile in CPFE lungs is essentially identical to lungs from patients with IPF. These data suggest that distinct inflammatory processes collectively contribute to the disease processes in patients with emphysema, when compared to IPF and CPFE.

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.

Background: Patients with pulmonary hypertension (PH) in respiratory disease (group 3 PH) have adverse outcomes. Some studies suggest that patients with more severe PH (mPAP≥35mmHg) benefit from sildenafil use. Aims: To assess short term outcomes following sildenafil use in patients with severe group 3 PH. Methods: Patients from the Royal Brompton Hospital were assessed at baseline and 3-6 month follow-up using right heart catheterisation (RHC), echocardiography, brain natriuretic peptide (BNP), 6-minute walk test (6MW) and a PH-specific quality of life score (EmPHasis-10, E10). Other contributing factors to PH were excluded. Sildenafil was initiated at 12.5-25mg TDS. Data are mean±SD or median (IQR). Results: Patients (n=18) were 50% male, 63.5±11.3 years with ILD (n=8), combined pulmonary fibrosis and emphysema (n=3), COPD (n=4) and sleep disorders (n=3), had FEV1 64.3±30.9%, FVC 73.8±33.4%, FEV/FVC 71.7±16.9%, TLCO 22.4±6.4% and KCO 47.5±33.8% predicted. RHC showed mPAP 47.4±11.0mmHg, PCWP 9±4mmHg and PVR 10.7±5.1 Wood units. 3/18 did not tolerate sildenafil (hypotension, no benefit, unmasking of diastolic dysfunction). At 3-6 months, BNP fell from 699±646 to 451±450, p=0.02, E10 improved from 37±10 to 29±12, p=0.002. WHO functional class improved, p=0.054 (Figure A-D). Conclusion: Sildenafil was well tolerated in patients with severe group 3 PH, with improved WHO FC, BNP and quality of life, and a good safety signal. Larger studies are warranted.

Background: Idiopathic pulmonary fibrosis (IPF) and combined pulmonary fibrosis with emphysema (CPFE) are associated with an increased risk of pulmonary hypertension (PH). Few data are available regarding PH severity and correlation with respiratory physiology. Aim: To evaluate baseline respiratory and hemodynamic characteristics of patients with IPF-PH and CPFE-PH. Methods: Patients with a diagnosis of IPF or CPFE were analysed from a prospective multicenter observational study (HYPID) conducted in French expert centers for rare pulmonary diseases and/or PH (NCT01443598). Severe PH was defined as mean pulmonary artery pressure (mPAP) > 35 mmHg or cardiac index (CI) Results: Out of 220 patients included in the cohort, 61 had IPF-PH and 75 CPFE-PH. Patients were 74% males, with a mean age of 69 ± 9 years. The mean FVC at baseline was 75 ± 25%, and mean DLco was 25 ± 10%. NYHA class was I-II in 18% of patients, III in 56%, IV in 24%, N/A in 2%. Six-min walk distance was 276 ± 145 m. Hemodynamic characteristics were mPAP 38 ± 9 mmHg, CI 2.5 ± 0.6 L/min/m², and pulmonary vascular resistance (PVR) 8.7 ± 3 WU. Kco was lower in CPFE-PH than in IPF-PH (table); other parameters were comparable between groups. DLco at baseline significantly correlated with mPAP (p=0.01 in IPF and 0.04 in CPFE group). DLco also correlated with PVR and CI in IPF-PH (p=0.001 and 0.01 respectively), but not in CPFE-PH. Conclusion: Hemodynamic severity is comparable in patients with IPF-PH and CPFE-PH, and correlates with DLco. Further study is needed to evaluate the prognostic significance of hemodynamic severity.

Combined pulmonary fibrosis and emphysema (CPFE) patients visit hospitals frequently due to acute exacerbations (AEs); however, the predictors of CPFE AE have not been comprehensively described in literature. Thus, we investigated the predicting factors of AE in CPFE patients. We retrospectively reviewed medical records from the past 12 years at Korea University Guro Hospital. We selected CPFE patients by computed tomography findings. Rapid deterioration (RD) was defined as acute worsening of dyspnea requiring hospitalization and the presence of newly developed radiologic abnormalities. AE was defined as RD with newly acquired bilateral pulmonary infiltrates without evidence of pulmonary infection or other known causes. We evaluated the following variables in CPFE patients: age, sex, smoking history and amount, body mass index, past medical history, pulmonary function test, gender, age, and physiology (GAP) score, and the presence of lung cancer. Among 227 CPFE patients, 108 had RD and 31 developed AE. The most common cause of RD was infection (n = 60, 55.6%) and 28.7% (n = 31) developed AE. Lung cancer [hazard ratio (HR), 3.274; 95% confidence interval (95% CI) 1.444–7.425; P

Background Interstitial lung disease (ILD) is a possible manifestation of several rheumatic diseases. Although lung involvement is common in Anti-neutrophil cytoplasmic antibodies (ANCA) vasculitides (AAV), the presence of ILD is relatively rare. Moreover, a very small subgroup of patients may present ILD along ANCA positivity without other systemic signs of AAV. Objectives To describe the phenotypic characteristics of ILD patients with ANCA positivity without a definite diagnosis of AAV. Methods ANCA-ILD patients from 7 tertiary care hospitals (6 from Italy, 1 from Spain – 2 rheumatology centres, 4 pneumology centres, 1 internal medicine) were included. The mean follow-up was of 62.6±49.8 months. We collected epidemiologic, demographic, clinical, serological, pulmonary function test (PFT) data and high resolution computed tomography (HRCT) pattern. Results 19 patients with ANCA-ILD (M:F=9:10, mean age at diagnosis 66.2±8 years) were enrolled. The mean latency between the first respiratory symptom onset and the diagnosis was 26.4±37.0 months. Sixteen patients (84%) had ANCA-MPO positivity while 3 ANCA-PR3. Antinuclear autoantibodies were positive in 12 patients (63%). Usual interstitial pneumonia was the main HRCT pattern (10, 52.6%), followed by non specific interstitial pneumonia (8, 42%, 1 associated with organising pneumonia), 1 combined pulmonary fibrosis and emphysema. Six patients with ILD-ANCA presented also a non-erosive oligoarticular inflammation (n=6). During the follow-up, the majority of the patients (16/19) did not require oxygen therapy at last evaluation. However, 1 patient required continuous O2, 1 intermittent O2, 1 patient underwent lung transplant due to respiratory failure. Five patients required hospitalisation due to respiratory insufficiency. Two patients died, both for respiratory insufficiency. All patients were treated with glucocorticoids as induction therapy (4 intravenous pulses), combined with an immunosuppressant in 11 cases: cyclophosphamide (3, 15%), azathioprine (6, 31%), mycophenolate (2, 10.5%), methotrexate (1, 5.5%) or rituximab (2, 10.5%). Conclusions the observation of ANCA positivity in patients with ILD may open new prospective in the assessment of interstitial lung diseases. Although most of patients had a good prognosis, up to 25% presented unfavourable respiratory outcome. Further prospective studies in larger cohorts and longer follow-up may clarify the prognosis of this particular lung disease and if ILD-ANCA should be classified as a distinct subset or an incomplete form of AAV. Disclosure of Interest None declared

The purpose of this study was to clarify the clinicopathologic characteristics of non-small cell lung cancer (NSCLC) patients with combined pulmonary fibrosis and emphysema (CPFE). We investigated the association between CPFE, the cancer survival, and the pathological features of clinical stage I NSCLC patients. Between 2005 and 2014, 218 consecutive patients with clinical stage I NSCLC underwent complete resection with systematic lymph node dissection. A univariate analysis by log-rank tests was performed to determine the risk factors for recurrence, and the Cox proportional hazards regression model was used to identify potential independent predictors. The 5-year recurrence-free proportion of patients with CPFE was 36%, which was significantly lower than in those without CPFE (82%; p

Cigarette smoke is recognized as the primary causative agent of certain interstitial lung diseases (ILDs), namely respiratory bronchiolitis–associated ILD, desquamative interstitial pneumonia, and pulmonary Langerhans cell histiocytosis. Cigarette smoking is also responsible for some cases of acute eosinophilic pneumonia and appears to be a risk factor for the development of idiopathic pulmonary fibrosis and rheumatoid arthritis–associated ILD. Some smokers with emphysema develop a superimposed fibrotic process resulting in combined pulmonary fibrosis and emphysema syndrome associated with preserved lung volumes. Smoking cessation should occupy a pivotal role in the management of all smokers with these diffuse lung diseases.

Traditionally recognized smoking-related lung diseases include chronic obstructive pulmonary disease (COPD), respiratory bronchiolitis/interstitial lung disease, desquamative interstitial pneumonitis, and pulmonary Langerhans cell histiocytosis. More recently described smoking-related entities include combined pulmonary fibrosis and emphysema and respiratory bronchiolitis with fibrosis. We review the important past and current literature pertaining to these diseases, including recent developments in quantitative imaging of COPD and in CT characterization of smoking-related fibrosis.

Decreased bone mineral density (BMD) has been reported in patients with interstitial lung disease. However, BMD has not been evaluated in steroid-naïve patients with idiopathic pulmonary fibrosis (IPF). We aimed to measure vertebral BMD and investigate its relationship with clinical features in steroid-naïve patients with IPF.We recruited 55 consecutive male patients with steroid-naïve IPF; 55 male smokers without chronic obstructive pulmonary disease or interstitial lung disease, matched by age, body mass index, and pack-years of smoking (control smokers); and 27 healthy young adults. Thoracic vertebral BMD was measured by computed tomography (CT). We further investigated the relationship of BMD with clinical features and quantitative CT indices of lung density in patients with IPF.The thoracic vertebral BMD of patients with IPF was significantly lower than that of control smokers (139.9 ± 28.5 mg/mL vs 160.9 ± 39.5 mg/mL, p0.01). Fifteen patients (27.2%) had BMD more than 2.5 SD below the mean BMD of young adults. In patients with IPF, emphysema volume (EV) and its ratio to total lung volume (EV%) had a significantly negative correlation with BMD (r = -0.28, p = 0.04 and r = -0.39, p0.01, respectively). In stepwise multiple regression analysis, EV% was an independent explanatory variable for thoracic vertebral BMD.A substantial percentage of steroid-naïve IPF patients had decreased BMD, and a significant association was observed between the extent of emphysema and BMD in IPF.

We report an educational autopsy case of combined pulmonary fibrosis and emphysema. Radiological patterns of the upper lung were considered as mostly emphysema, but pathological observation revealed significant interstitial fibrosis of usual interstitial pneumonia as a major pathology. The patient eventually developed acute exacerbation of background interstitial pneumonia. Careful radiological and pathological correlation of the current case indicates that regions with distal acinar emphysema on computed tomography image may possess histologically marked dense fibrosis of lethal interstitial pneumonia., International Journal of Chronic Obstructive Pulmonary Disease, 10(1), pp.1299-1303; 2015

The combined pulmonary fibrosis and emphysema (CPFE) syndrome is a unique and an under-recognized disorder characterized by emphysema in the upper lobes and interstitial fibrosis in the lower lobes of the lung. It occurs predominantly in males and almost exclusively in smokers. This rare combination of a restrictive and an obstructive mechanical defect carries a poorer prognosis than either of the two components. We present a case of CPFE syndrome in a non-smoker female patient who developed lower lobe emphysema subsequent to development of interstitial fibrosis. The case was remarkable for the extreme rarity of several presenting features, namely, a lower lobe occurrence of emphysema subsequent to pre-existent interstitial fibrosis, female gender and absence of a history of smoking.

For many years, cigarette smoking has been considered as the leading cause of chronic obstructive pulmonary disease and lung cancer. Recently, however, it has also been associated with the development of diffuse interstitial lung diseases. In the latest classification of the major idiopathic interstitial pneumonias (IIP), the term smoking-related IIP has been introduced, including two entities, namely desquamative interstitial pneumonia (DIP) and respiratory bronchiolitis-interstitial lung disease (RB-ILD). Other entities in which smoking has a definite or suggested role include pulmonary Langerhan's cell histiocytosis, smoking-related interstitial fibrosis, combined pulmonary fibrosis and emphysema syndrome and idiopathic pulmonary fibrosis. In this review, we will focus on the mechanisms of smoking-related lung damage and on the clinical aspects of these disorders with the exception of idiopathic pulmonary fibrosis, which will be reviewed elsewhere in this review series.