Combined pulmonary fibrosis and emphysema and idiopathic pulmonary fibrosis in non-small cell lung cancer: impact on survival and acute exacerbation.
ABSTRACT: 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 < 0.001), and lower forced expiratory volume in 1 s. Of all patients with NSCLC, 71.7% overall died during the follow-up period; 71.6% died in the CPFE group and 72.0% in the IPF group. Multivariate logistic regression analysis showed that CPFE (odds ratio [OR]: 2.26, 95% confidence interval [CI]: 1.09-4.69; 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.
Project description: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.
Project description: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.
Project description:Little has been reported on the feasibility of xenon-enhanced dual-energy computed tomography (Xe-DECT) in the visual and quantitative analysis of combined pulmonary fibrosis and emphysema (CPFE).We compared CPFE with idiopathic pulmonary fibrosis (IPF) and chronic obstructive pulmonary disease (COPD), as well as correlation with parameters of pulmonary function tests (PFTs).Studied in 3 groups were 25 patients with CPFE, 25 with IPF without emphysema (IPF alone), 30 with COPD. Xe-DECT of the patients' entire thorax was taken from apex to base after a patient's single deep inspiration of 35% stable nonradioactive xenon. The differences in several parameters of PFTs and percentage of areas enhanced by xenon between 3 groups were compared and analyzed retrospectively.The percentage of areas enhanced by xenon in both lungs were calculated as CPFE/IPF alone/COPD = 72.2 ± 15.1% / 82.2 ± 14.7% /45.2 ± 23.2%, respectively. In the entire patients, the percentage of areas enhanced by xenon showed significantly a positive correlation with FEV1/FVC (R = 0.558, P < 0.0001) and %FEV1, (R = 0.528, P < 0.0001) and a negative correlation with %RV (R = -0.594, P < 0.0001) and RV/TLC (R = -0.579, P < 0.0001). The percentage of areas enhanced by xenon in patients with CPFE showed significantly a negative correlation with RV/TLC (R = -0.529, P = 0.007). Xenon enhancement of CPFE indicated 3 different patterns such as upper predominant, diffuse, and multifocal defect. The percentage of areas enhanced by xenon in upper predominant defect pattern was significantly higher than that in diffuse defect and multifocal defect pattern among these 3 different patterns in CPFE.The percentage of areas enhanced by xenon demonstrated strong correlations with obstructive ventilation impairment. Therefore, we conclude that Xe-DECT may be useful for distinguishing emphysema lesion from fibrotic lesion in CPFE.
Project description:Combined idiopathic pulmonary fibrosis (IPF) with pulmonary emphysema (CPFE) is a syndrome with a characteristic presentation of upper lobe emphysema and lower lobe fibrosis. While CPFE is a strong determinant of secondary precapillary pulmonary hypertension (PH), there is limited evidence regarding the management of patients with CPFE and PH.A 63 year-old male presented in 2006 with dyspnoea on exertion having quit smoking in 2003. Clinical examination, together with high resolution computed tomography, bronchoalveolar lavage, and echocardiographic assessments, suggested a diagnosis of CPFE without PH. In 2007, the patient received intravenous cyclophosphamide, N-acetylcysteine, and short-term anticoagulation treatment. Due to remission of acute exacerbations, the patient received triple combination therapy (prednisone, N-acetylcysteine and azathioprine). Upon progressive clinical worsening, long-term supplemental oxygen therapy was initiated in 2009. Repeated right heart catheterisation in 2011 confirmed PH and worsening pulmonary haemodynamics, and off-label ambrisentan therapy was initiated. Dyspnoea remained at follow-up, although significant haemodynamic improvement was observed.CFPE is a distinct but under-recognized and common syndrome with a characteristic presentation. Further studies are needed to ascertain the etiology, morbidity, and mortality of CPEF with or without PH, and to evaluate novel management options.
Project description:Purpose:Current guidelines recommend definitive radiotherapy for patients with medically inoperable early-stage non-small cell lung cancer (NSCLC). However, the impact of underlying pulmonary diseases on survival in those patients remains unclear. Methods:We retrospectively reviewed the medical records of 234 patients with stage I-II NSCLC treated with definitive radiotherapy alone at Samsung Medical Center between January 2010 and October 2017. We compared survival outcomes according to the presence of underlying pulmonary diseases, including chronic obstructive pulmonary disease (COPD), combined pulmonary fibrosis and emphysema (CPFE), and idiopathic pulmonary fibrosis (IPF). The control group in this study was stage I-II NSCLC patients who were non-COPD, non-CPFE, and non-IPF. Results:The median follow-up duration was 17 (range, 1-92) months. The median survival times of the control, COPD, CPFE, and IPF groups were 32, 49, 17, and 12 months, respectively (P<0.001). In a Cox proportional hazards analysis for factors associated with overall survival, patients with COPD showed a similar risk of death (adjusted hazard ratio [HR], 1.306; 95% confidence interval [CI], 0.723-2.358; P=0.376) compared to that of the control group, while patients with CPFE (adjusted HR, 3.382; 95% CI, 1.472-7.769; P=0.004) and IPF (adjusted HR, 4.061; 95% CI, 1.963-8.403; P<0.001) showed an increased risk of death. Conclusion:Definitive radiotherapy may be a tolerable treatment for early-stage NSCLC with COPD. However, poor survival in early-stage NSCLC patients with IPF or CPFE requires further study to identify and develop patient selection criteria as well as an optimal radiotherapy modality.
Project description:Our purpose was to assess the clinical data, predictors of mortality and acute exacerbation (AE) in combined pulmonary fibrosis and emphysema (CPFE) patients.Single-centre retrospective cohort study.Teaching hospital in Japan.We identified 93 CPFE patients with high-resolution computed tomographic (HRCT) through multidisciplinary discussion. Patients who had connective tissue disease, drug-associated interstitial lung disease and occupationally related interstitial lung disease, such as asbestosis and silicosis, were excluded.There were no interventions.Medical records and HRCT scans from January 2002 through December 2007 were reviewed retrospectively at our hospital. Ninety-three patients had CPFE.The mean age of CPFE patients was 74 years. Idiopathic pulmonary fibrosis and non-specific interstitial pneumonia were observed as distinct HRCT patterns. Forty-two patients showed finger clubbing. Mean serum Krebs von den Lungen-6 (KL-6) and per cent predicted forced vital capacity (%FVC) were 1089 IU/l, 63.86%, respectively. Twenty-two patients developed AE during observation period. Baseline KL-6 was a strong predictor of AE (OR=1.0016, p=0.009). Finger clubbing (HR=2.2620, p=0.015) and per cent predicted forced expiratory volume in one second/%FVC more than 1.2 (HR=1.9259, p=0.048) were independent predictors of mortality in CPFE.Baseline serum KL-6 was a useful predictor of AE (cut-off =1050, receiver operator characteristic curve: 0.7720), which occurred in 24% (22/93) of the CPFE patients. Finger clubbing and per cent predicted forced expiratory volume in one second/%FVC more than 1.2 were independent predictors of mortality.
Project description:A 30-year-old male smoker with congenital amblyopia and oculocutaneous albinism was admitted to our hospital complaining of progressive dyspnea on exertion. Chest computed tomography images revealed diffuse reticular opacities and honeycombing in the bilateral lower lobes with sparing of the subpleural region along with emphysema predominantly in the upper lobes. Lung biopsy specimens showed a mixture of usual interstitial pneumonia and a non-specific interstitial pneumonia pattern with emphysema. Of note, cuboidal epithelial cells with foamy cytoplasm on the alveolar walls and phagocytic macrophages with ceroid pigments in the fibrotic lesions were observed. The patient was diagnosed with Hermansky-Pudlak syndrome (HPS) associated with combined pulmonary fibrosis and emphysema (CPFE). Six years following the patient's initial admission to our hospital, he died from acute exacerbation (AE) of CPFE associated with HPS. This is one of only few reports available on the clinicopathological characteristics of AE in CPFE associated with HPS.
Project description:There is increasing clinical, radiologic, and pathologic recognition of the coexistence of emphysema and pulmonary fibrosis in the same patient, resulting in a clinical syndrome known as combined pulmonary fibrosis and emphysema (CPFE) that is characterized by dyspnea, upper-lobe emphysema, lower-lobe fibrosis, and abnormalities of gas exchange. This syndrome frequently is complicated by pulmonary hypertension, acute lung injury, and lung cancer. The CPFE syndrome typically occurs in male smokers, and the mortality associated with this condition, especially if pulmonary hypertension is present, is significant. In this review, we explore the current state of the literature and discuss etiologic factors and clinical characteristics of the CPFE syndrome.
Project description: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.
Project description:Acute exacerbation (AE) of idiopathic pulmonary fibrosis (IPF) results in poor survival. The objective of the present study was to elucidate the impact of asymmetrical ground-glass opacity (GGO) and/or consolidation on outcomes in patients with AE-IPF. The cases of 59 consecutive patients with AE-IPF were retrospectively reviewed. High-resolution computed tomography (HRCT) at diagnosis of an AE was assessed to determine the disease extent and asymmetry. Asymmetrical AE was defined as a right-to-left ratio of GGO and consolidation ≥2.0 or ≤0.5. The impacts of HRCT indices and other clinical parameters on 180-day mortality were analysed. The overall 180-day mortality rate was 59.2%, and asymmetrical AE was observed in 13 patients (22.0%). A multivariate analysis revealed that asymmetrical AE was a significant predictor of 180-day mortality (hazard ratio=0.36, p=0.047), long-term oxygen therapy before AE and serum lactate dehydrogenase levels. The 180-day mortality of patients with asymmetrical AE was significantly lower than that of patients with symmetrical AE (asymmetrical AE 30.8% versus symmetrical AE 68.2%, p=0.03). An asymmetrical distribution of GGO and/or consolidation is a predictor of survival in patients with AE-IPF.