BACKGROUND Lung cancer (LC) is frequently associated with idiopathic pulmonary fibrosis (IPF). Despite this well-known association, the outcome of LC in patients with IPF is unclear. The objective of ...this study was to evaluate the impact of LC on survival of patients with associated IPF. METHODS A total of 260 patients with IPF were reviewed, and 186 IPF cases had complete clinical and follow-up data. Among these, five cases were excluded because LC was radiologically suspected but not histologically proven. The remaining 181 cases were categorized in two groups: 23 patients with biopsy-proven LC and IPF (LC-IPF) and 158 patients with IPF only (IPF). Survival and clinical characteristics of the two groups were compared. RESULTS Prevalence of histologically proven LC was 13%, and among those with LC-IPF cumulative incidence at 1 and 3 years was 41% and 82%. Patients with LC were more frequently smokers (91.3% vs 71.6%, P = .001), with combined pulmonary fibrosis and emphysema (52% vs 32%, P = .052). Survival in patients with LC-IPF was significantly worse than in patients with IPF without LC (median survival, 38.7 months vs 63.9 months; hazard ratio = 5.0; 95% CI, 2.91-8.57; P < .001). Causes of death in the study group were respiratory failure in 43% of patients, LC progression in 13%, and LC treatment-related complications in 17%. CONCLUSIONS In patients with IPF, LC has a significant adverse impact on survival. Diagnosis and treatment of LC in IPF are burdened by an increased incidence of severe complicating events, apparently as lethal as the cancer itself.
Surgical lung biopsy is often required for a confident multidisciplinary diagnosis of idiopathic pulmonary fibrosis (IPF). Alternative, less-invasive biopsy methods, such as bronchoscopic lung ...cryobiopsy (BLC), are highly desirable.
To address the impact of BLC on diagnostic confidence in the multidisciplinary diagnosis of IPF.
In this cross-sectional study we selected 117 patients with fibrotic interstitial lung disease without a typical usual interstitial pneumonia pattern on high-resolution computed tomography. All cases underwent lung biopsies: 58 were BLC, and 59 were surgical lung biopsy (SLB). Two clinicians, two radiologists, and two pathologists sequentially reviewed clinical-radiologic findings and biopsy results, recording at each step in the process their diagnostic impressions and confidence levels.
We observed a major increase in diagnostic confidence after the addition of BLC, similar to SLB (from 29 to 63%, P = 0.0003 and from 30 to 65%, P = 0.0016 of high confidence IPF diagnosis, in the BLC group and SLB group, respectively). The overall interobserver agreement in IPF diagnosis was similar for both approaches (BLC overall kappa, 0.96; SLB overall kappa, 0.93). IPF was the most frequent diagnosis (50 and 39% in the BLC and SLB group, respectively; P = 0.23). After the addition of histopathologic information, 17% of cases in the BLC group and 19% of cases in the SLB group, mostly idiopathic nonspecific interstitial pneumonia and hypersensitivity pneumonitis, were reclassified as IPF.
BLC is a new biopsy method that has a meaningful impact on diagnostic confidence in the multidisciplinary diagnosis of interstitial lung disease and may prove useful in the diagnosis of IPF. This study provides a robust rationale for future studies investigating the diagnostic accuracy of BLC compared with SLB.
A diagnosis of interstitial lung diseases (ILDs) may include surgical lung biopsy (SLB), which is associated with significant morbidity and mortality and also appreciable costs. Transbronchial lung ...cryobiopsy (TBLC) is adopting an important role.
The aim of this study was to compare the diagnostic yield (DY) and safety of TBLC and SLB in a large cohort of patients and to perform a systematic review of the literature as well as a meta-analysis.
We performed a retrospective analysis of 447 cases with ILD undergoing TBLC and/or SLB and a systematic review of the literature (MEDLINE and Embase for all original articles on the DY and safety of TBLC in ILDs up to July 2015).
A total of 150 patients underwent SLB and 297 underwent TBLC. The median time of hospitalization was 6.1 days (SLB) and 2.6 days (TBLC; p < 0.0001). Mortality due to adverse events was observed for 2.7% (SLB) and 0.3% (TBLC) of the patients. Pneumothorax was the most common complication after TBLC (20.2%). No severe bleeding was observed. TBLC was diagnostic for 246 patients (82.8%), SLB for 148 patients (98.7%, p = 0.013). A meta-analysis of 15 investigations including 781 patients revealed an overall DY of 0.81 (0.75-0.87); the overall pooled probability of developing a pneumothorax, as retrieved from 15 studies including 994 patients, was 0.06 (95% CI 0.02-0.11).
Cryobiopsy is safe and has lower complication and mortality rates compared to SLB. TBLC might, therefore, be considered the first diagnostic approach for obtaining tissue in ILDs, reserving the surgical approach for cases in which TBLC is not diagnostic.
Histology is a key element for the multidisciplinary diagnosis of fibrotic diffuse parenchymal lung diseases (f-DPLD) when the clinical-radiological picture is nondiagnostic. Transbronchial lung ...cryobiopsy (TBLC) have been shown to be useful for obtaining large and well-preserved biopsies of lung parenchyma, but experience with TBLC in f-DPLD is limited.
To evaluate safety, feasibility and diagnostic yield of TBLC in f-DPLD.
Prospective study of 69 cases of TBLC using flexible cryoprobe in the clinical-radiological setting of f-DPLD with nondiagnostic high resolution computed tomography (HRCT) features.
pneumothorax occurred in 19 patients (28%). One patient (1.4%) died of acute exacerbation. Feasibility: adequate cryobiopsies were obtained in 68 cases (99%). The median size of cryobiopsies was 43.11 mm(2) (range, 11.94-76.25). Diagnostic yield: among adequate TBLC the pathologists were confident ("high confidence") that histopathologic criteria sufficient to define a specific pattern in 52 patients (76%), including 36 of 47 with UIP (77%) and 9 nonspecific interstitial pneumonia (6 fibrosing and 3 cellular), 2 desquamative interstitial pneumonia/respiratory bronchiolitis-interstitial lung disease, 1 organizing pneumonia, 1 eosinophilic pneumonia, 1 diffuse alveolar damage, 1 hypersensitivity pneumonitis and 1 follicular bronchiolitis. In 11 diagnoses of UIP the pathologists were less confident ("low confidence"). Agreement between pathologists in the detection of UIP was very good with a Kappa coefficient of 0.83 (95% CI, 0.69-0.97). Using the current consensus guidelines for clinical-radiologic-pathologic correlation 32% (20/63) of cases were classified as Idiopathic Pulmonary Fibrosis (IPF), 30% (19/63) as possible IPF, 25% (16/63) as other f-DPLDs and 13% (8/63) were unclassifiable.
TBLC in the diagnosis of f-DPLD appears safe and feasible. TBLC has a good diagnostic yield in the clinical-radiological setting of f-DPLD without diagnostic HRCT features of usual interstitial pneumonia. Future studies should consider TBLC as a potential alternative to SLBx in f-DPLD.
Idiopathic pulmonary fibrosis (IPF) is a specific form of chronic, progressively fibrosing interstitial pneumonia that is associated with a significantly worse prognosis than other forms of chronic ...interstitial pneumonia. An early and accurate diagnosis of IPF is important to enable the initiation of disease-specific therapies, which have the potential to reduce disease progression, and the avoidance of inappropriate and potentially harmful drugs. Establishing an accurate diagnosis of IPF can be challenging. Recent studies and international guidelines advocate the importance of a multidisciplinary team (MDT) in the initial diagnostic assessment of patients with suspected IPF. Typical MDT members include a pulmonologist, a radiologist and a pathologist, with further input from a thoracic surgeon, a rheumatologist, a specialist nurse and an occupational physician where appropriate. Multidisciplinary diagnosis is considered the gold standard because it can improve the accuracy of diagnosis of IPF, avoid unnecessary testing (e.g. lung biopsy), and optimise patient management. Here we highlight the strengths and limitations of the multidisciplinary approach to IPF diagnosis through MDT discussion of two patient cases.
Usual interstitial pneumonia (UIP), is a necessary feature pathologically or radiologically for the diagnosis of idiopathic pulmonary fibrosis (IPF). The predictive value of transbronchial biopsy ...(TBB) in identifying UIP is currently unknown. The objective of this study is to assess the accuracy with which histopathologic criteria of usual interstitial pneumonia (UIP) can be identified in transbronchial biopsy (TBB) and to assess the usefulness of TBBx in predicting a the diagnosis of UIP pattern. We conducted a retrospective blinded and controlled analysis of TBB specimens from 40 established cases of UIP and 24 non-UIP interstitial lung diseases.
Adequate TBB specimens were available in 34 UIP cases (85% of all UIP cases). TBB contained histopathologic criteria to suggest a UIP pattern (ie. at least one of three pathologic features of UIP present; patchy interstitial fibrosis, fibroblast foci, honeycomb changes) in 12 cases (30% of all UIP cases). Sensitivity, specificity, positive and negative predictive values for the two pathologists were 30% (12/40), 100% (24/24), 100% (12/12), 46% (24/52) and 30% (12/40), 92% (22/24), 86% (12/14), 55% (22/40) respectively. Kappa coefficient of agreement between pathologists was good (0.61, 95% CI 0.31-0.91). The likelihood of identifying UIP on TBB increased with the number and size of the TBB specimens.
Although sensitivity is low our data suggest that even modest amount of patchy interstitial fibrosis, fibroblast foci, honeycomb changes detected on TBB can be highly predictive of a UIP pattern. Conversely, the absence of UIP histopathologic criteria on TBB does not rule out UIP.
Idiopathic pulmonary fibrosis (IPF) is the most common type of idiopathic interstitial pneumonia and has a dismal prognosis. Median age at IPF onset is 60-70 years and it is mainly related to ...cigarette smoke exposure. Its clinical profile is heterogeneous and different clinical phenotypes are now better defined: familial IPF, slow and rapid progressors, combined pulmonary fibrosis and emphysema, anti-neutrophil cytoplasmic antibodies/microscopic polyangiitis and IPF, and IPF associated with lung cancer. Acute exacerbation associated with rapid functional decline is an event that does not happen infrequently and affects survival. Diagnosis requires a typical usual interstitial pneumonia (UIP) pattern on computed tomography in the appropriate clinical setting or morphological confirmation of the UIP pattern when imaging findings are not characteristic enough. Surgical lung biopsy is the gold standard to obtain valuable information for histological analysis. However, less invasive procedures (transbronchial lung biopsy or even improved transbronchial lung biopsy by cryoprobes) are now under consideration. Prognostic indicators are mainly derived by pulmonary function tests. Recently, staging systems have been proposed.
Transbronchial lung cryobiopsy is an innovative method of obtaining samples from the parenchyma of patients with diffuse parenchymal lung diseases. However, the technique is not yet standardized, and ...uncertainty exists about the optimal protocol, including the number of samples, the biopsy size, and the choice of the biopsy site.
To compare the diagnostic yield and complications of cryobiopsy with different strategies adopted to sample lung tissue (number of samples, biopsy site, and sample size).
We prospectively enrolled 46 patients with suspected diffuse parenchymal lung diseases for the diagnosis of which a biopsy was deemed useful. All patients underwent transbronchial lung cryobiopsy, and they were randomly assigned to group A (4 samples obtained from the same segment) or group B (2 samples obtained from one segment and 2 samples obtained from a different segment of the same lobe). Analysis of the samples was performed sequentially (from the first to the last sample), and pathologists reformulated their histopathologic diagnosis with the addition of each sample.
The mean diagnostic yield of the procedure combining the 2 groups and performing only the first sampling was 69%. When a second biopsy was performed as well, the mean diagnostic yield improved, but this increase was significant only when the 2 samples were obtained from 2 different segments (96%, group B).
This study suggests that the strategy of performing 2 biopsies with a cryoprobe may be associated with an increased diagnostic yield in diffuse parenchymal lung diseases if these samples are obtained from 2 different segments within the same lobe.
Purpose
Sleep Breathing Disorders (SBD) are frequently found in idiopathic pulmonary fibrosis (IPF) and they are associated with worse quality of sleep and life and with higher mortality. The study ...aimed at evaluating the impact of SBD on prognosis (mortality or disease progression) in 35 patients with mild to moderate IPF.
Methods and Results
Obstructive sleep apnea (OSA) was diagnosed in 25/35 patients with IPF: 14/35 mild, 7/35 moderate, and 4/35 severe. According to the American Academy of Sleep Medicine (AASM) definition, sleep-related hypoxemia was found in 9/35 patients with IPF. According to the presence/absence of SBD, IPF patients were divided into 4 groups: NO-SBD group (Group A, 25.7%), OSA without sleep-related hypoxemia (Group B, 48.5%), OSA with sleep-related hypoxemia group (Group C, 22.8%), and only 1/35 had sleep-related hypoxemia without OSA(Group D, 2.8%). Statistical analysis was focused only on group A, B, and C. Patients with OSAS and sleep-related hypoxemia (Group C) had the worse prognosis, both in terms of mortality or clinical deterioration. SBD were the only independent risk factor (Cox Proportional Hazards Multiple Regression Analysis) for mortality (HR 7.6% IC 1.2–36.3;
p
= 0.029) and disease progression (HR 9.95% IC 1.8–644.9;
p
= 0.007).
Conclusions
SBD are associated with a worse prognosis, both in terms of mortality or clinical progression. The presence of SBD should be explored in all IPF patients.
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