Search

Combined Pulmonary Fibrosis and Emphysema (CPFE) refers to the coexistence of upper lobe predominant emphysema with diffuse pulmonary fibrosis, mainly in the lower lobes. Although initially described in patients with Idiopathic Pulmonary Fibrosis (IPF), since then it has been described in other forms of pulmonary fibrosis, most notably collagen tissue disorder associated interstitial lung diseases. High Resolution Computed Tomography (HRCT) has a pivotal role in diagnosis. Recognizing CPFE is not an academic exercise but has significant clinical implications. Thus, it is important for the treating physician to be familiarized with the radiological characteristics that will establish diagnosis. In this review we will discuss the special physiologic and radiological features of CPFE, the challenges in monitoring the course of the disease, the natural history and also the clinical importance of potential complications.

Background Combined pulmonary fibrosis and emphysema (CPFE) is an umbrella term encompassing upper lobe emphysema and lower lobe pulmonary fibrosis with pathogenesis elusive. The aim of our study was to investigate the incidence of autoimmune markers in patients with CPFE. Methods In this multicenter study we retrospectively evaluated records from patients with CPFE (n=40) and IPF (n=60) without emphysema. Baseline demographic characteristics, high-resolution computed tomography (HRCT), spirometry, histopathological, treatment, serum immunologic and survival data were investigated. B cell presence was estimated with CD20 immunostaining in representative lung biopsy samples from CPFE patients and control subjects. Results A statistically significant increased number of CPFE patients with elevated serum ANA with or without positive p-ANCA titers compared to patients with IPF without emphysema was observed. Patients with CPFE and positive autoimmune markers exhibited improved survival compared to patients with a negative autoimmune profile. A massive infiltration of clusters of CD20+ B cells forming lymphoid follicles within the fibrotic lung in CPFE patients with positive serum immunologic profile compared to patients with negative profile, was noted and positively correlated with improved survival. Conclusions A significant proportion of patients with CPFE may present with underlying auto-immune disorders that may reside insidiously and be associated with favorable prognosis. Early identification of these patients using a panel of auto-antibodies may lead to more targeted and effective therapeutic applications.

Purpose Quantitative analysis of CT scans has proven to be a reproducible technique, which might help to understand the pathophysiology of chronic obstructive pulmonary disease (COPD) and combined pulmonary fibrosis and emphysema. The aim of this retrospective study was to find out if the lung function of patients with COPD with Global Initiative for Chronic Obstructive Lung Disease (GOLD) stages III or IV and pulmonary emphysema is measurably influenced by high attenuation areas as a correlate of concomitant unspecific fibrotic changes of lung parenchyma. Patients and methods Eighty-eight patients with COPD GOLD stage III or IV underwent CT and pulmonary function tests. Quantitative CT analysis was performed to determine low attenuation volume (LAV) and high attenuation volume (HAV), which are considered to be equivalents of fibrotic (HAV) and emphysematous (LAV) changes of lung parenchyma. Both parameters were determined for the whole lung, as well as peripheral and central lung areas only. Multivariate regression analysis was used to correlate HAV with different parameters of lung function. Results Unlike LAV, HAV did not show significant correlation with parameters of lung function. Even in patients with a relatively high HAV of more than 10%, in contrast to HAV (p=0.786) only LAV showed a significantly negative correlation with forced expiratory volume in 1 second (r=-0.309, R2=0.096, p=0.003). A severe decrease of DLCO% was associated with both larger HAV (p=0.045) and larger LAV (p=0.001). Residual volume and FVC were not influenced by LAV or HAV. Conclusion In patients with COPD GOLD stage III-IV, emphysematous changes of lung parenchyma seem to have such a strong influence on lung function, which is a possible effect of concomitant unspecific fibrosis is overwhelmed.

We thank Dr. Oba for his interest in and comments on the revised document of the Global Initiative for Chronic Obstructive Lung Disease (GOLD) (1). We acknowledge that there are limits to the evidence base for roflumilast, but find that there is sufficient evidence for improvement in lung function and reduction of exacerbations, as stated in the document. However, as the evidence is weaker than for other drug classes, and because of the less favorable side effect profile, we do not recommend roflumilast as a firstchoice therapy but rather as one of several alternative choices. The GOLD document also lists all the adverse effects of roflumilast mentioned by Dr. Oba. We are somewhat less encouraged by the effects of theophylline than Dr. Oba, but do list theophylline as another possible treatment, and to a broader range of patients. We also thank Dr. West for pointing out the limitations of using FEV1 alone and not considering the underlying pathophysiology leading to chronic bronchitis and/or emphysema—there is a significant proportion of patients with both. However, as we have no treatments aimed specifically at either of these disorders, we do not think a global document gains from “splitting” rather than “lumping” for management. We disagree with the statement that only subjects with reversible airway obstruction (at least measured as FEV1 reversibility) will benefit from bronchodilator treatment, and we therefore recommend a treatment trial with bronchodilators in patients with symptoms. As in medicine in general, this needs to be followed up, and patients who do not feel any benefit should of course not continue for symptomatic purposes alone. We believe that on a global scale, exposures other than smoking matter for the development of persistent airflow limitation, and we do not see any reason to highlight smoking here. And is chronic obstructive pulmonary disease (COPD) treatable? Yes, as treatment includes symptom management; not least, nonpharmacological treatment, such as pulmonary rehabilitation, has a major impact on symptoms and quality of life. Dr. Tzouvelekis and colleagues turn our attention to combined pulmonary fibrosis and emphysema. We also find the topic very interesting but find that our current knowledge on this entity does not warrant specific focus on combined pulmonary fibrosis and emphysema in the executive summary of a global COPD document. We hope that current and future research will enable us to better understand and manage this subgroup of patients with COPD.

BACKGROUND Pleuroparenchymal fibroelastosis (PPFE) has been described in hypersensitivity pneumonitis (HP) yet its functional implications are unclear. Combined pulmonary fibrosis and emphysema (CPFE) has occasionally been described in never-smokers with HP, but epidemiological data regarding its prevalence is sparse. CTs in a large HP cohort were therefore examined to identify the prevalence and effects of PPFE and emphysema. Methods 233 HP patients had CT extents of interstitial lung disease (ILD) and emphysema quantified to the nearest 5%. Lobar percentage pleural involvement of PPFE was quantified on a 4-point categorical scale: 0 = absent, 1 = affecting 33%. Marked PPFE reflected a total lung score of ≥3/18. Results were evaluated against FVC, DLco and mortality. RESULTS Marked PPFE prevalence was 23% whilst 23% of never-smokers had emphysema. Following adjustment for patient age, gender, smoking status, and ILD and emphysema extents, marked PPFE independently linked to reduced baseline FVC (p = 0.0002) and DLco (p = 0.002) and when examined alongside the same covariates, independently linked to worsened survival (p = 0.01). CPFE in HP demonstrated a characteristic functional profile of artificial lung volume preservation and disproportionate DLco reduction. CPFE did not demonstrate a worsened outcome when compared to HP patients without emphysema beyond that explained by CT extents of ILD and emphysema. CONCLUSIONS PPFE is not uncommon in HP, and is independently associated with impaired lung function and increased mortality. Emphysema was identified in 23% of HP never-smokers. CPFE appears not to link to a malignant microvascular phenotype as outcome is explained by ILD and emphysema extents.

Background Combined pulmonary fibrosis and emphysema (CPFE) is increasingly acknowledged as a separate syndrome with distinct clinical, physiological and radiological characteristics. We sought to identify physiologic and radiographic indices that predict mortality in CPFE. Methods Data on clinical characteristics, pulmonary function, high-resolution computed tomography (HRCT) and treatment were compared between patients with usual interstitial pneumonia (UIP) plus emphysema (CPFE group) and those with IPF alone (IPF group). Composite physiologic index (CPI) and HRCT scores at diagnosis and during follow-up were assessed. Results CPFE group (N = 87) was characterized by the predominance of males and smokers, who were less likely to have viral infection prior to the diagnosis, and display basal crackles, finger clubbing and wheeze, as compared to that in the IPF group (N = 105). HRCT and CPI scores increased over time in both groups. Moreover, CPFE group had a poorer prognosis, lower 5-year survival rate (43.42 % vs. 65.56 %; P 50 % received bronchodilators, 40 % received corticosteroids and 14 % needed noninvasive mechanical ventilation. On survival analyses, pulmonary arterial hypertension (PAH) and ≥ 5-point increase in CPI score per year were predictors of mortality in the CPFE group (hazard ratio [HR]: 10.29, 95 % Confidence Interval [CI]: 2.69–39.42 and HR: 21.60, 95 % CI: 7.28–64.16, respectively). Conclusion Patients with CPFE were predominantly male and smokers and exhibited distinct clinical, physiological and radiographic characteristics. They had a poorer prognosis than IPF. PAH and ≥ 5-point increase in CPI score per year were predictors of mortality in these patients. Future studies are needed to identify the optimal treatment approach to CPFE.

Background We hypothesized that, in patients with pulmonary fibrosis combined with emphysema, clinical characteristics and outcomes may differ from patients with pulmonary fibrosis without emphysema. We identified 102 patients who met established criteria for pulmonary fibrosis. The amount of emphysema (numerical score) and type of emphysema (centrilobular, paraseptal, or mixed) were characterized in each patient. Clinical characteristics, pulmonary function tests and patient survival were analysed. Results Based on the numerical emphysema score, patients were classified into those having no emphysema (n = 48), trivial emphysema (n = 26) or advanced emphysema (n = 28). Patients with advanced emphysema had a significantly higher amount of smoking in pack/years than patients with no emphysema or trivial emphysema (P < 0.0001). Median survival [1st, 3rd quartiles] of patients with advanced emphysema was 63 [36, 82] months compared to 29 [18, 49] months in patients without emphysema and 32 [19, 48] months in patients with trivial emphysema (P < 0.001). Median forced vital capacity (FVC) and total lung capacity (TLC) were higher in the advanced emphysema group compared to patients with no emphysema (P < 0.01 and P < 0.001, respectively), whereas median DLCO did not differ among groups and was overall low. Within the advanced emphysema group (n = 28), further characterization of the type of emphysema was performed and, within these subgroups of patients, survival was 75 [58, 85] months for patients with centrilobular emphysema, 75 [48, 85] months for patients with mixed centrilobular/paraseptal emphysema, and 24 [22, 35] months for patients with paraseptal emphysema (P < 0.01). Patients with advanced paraseptal emphysema had similar survival times to patients without emphysema. Conclusions Patients with pulmonary fibrosis combined with advanced centrilobular or mixed emphysema have an improved survival compared with patients with pulmonary fibrosis without emphysema, with trivial emphysema or with advanced paraseptal emphysema.