Surgical Lung Biopsy and Cryobiopsy in Fibrosing Interstitial Lung Diseases: One Swallow Does Not Make a Summer.
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ABSTRACT:
SUBMITTER: Bendstrup E
PROVIDER: S-EPMC6812444 | biostudies-literature | 2019 Oct
REPOSITORIES: biostudies-literature
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Surgical Lung Biopsy and Cryobiopsy in Fibrosing Interstitial Lung Diseases: One Swallow Does Not Make a Summer.
Bendstrup Elisabeth E Kronborg-White Sissel S Madsen Line Bille LB Rasmussen Torben R TR Folkersen Birgitte B Voldby Nina N Møller Janne J Poletti Venerino V
American journal of respiratory and critical care medicine 20191001 7
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Project description:BackgroundThe diagnostic accuracy and safety of transbronchial lung cryobiopsy (TBLC) via a flexible bronchoscope under sedation compared with that of surgical lung biopsy (SLB) in the same patients is unknown.MethodsRetrospectively the data of fifty-two patients with interstitial lung diseases (median age: 63.5 years; 21 auto-antibody positive) who underwent TBLC followed by SLB (median time from TBLC to SLB: 57 days) was collected. The samples from TBLC and SLB were randomly labelled to mask the relationship between the two samples. Diagnosis was made independently by pathologists, radiologists, and pulmonary physicians in a stepwise manner, and a final diagnosis was made at multidisciplinary discussion (MDD). In each diagnostic step the specific diagnosis, the diagnostic confidence level, idiopathic pulmonary fibrosis (IPF) diagnostic guideline criteria, and treatment strategy were recorded.ResultsWithout clinical and radiological information, the agreement between the histological diagnoses by TBLC and SLB was 42.3% (kappa [κ] = 0.23, 95% confidence interval [CI]: 0.08-0.39). However, the agreement between the TBLC-MDD and SLB-MDD diagnoses and IPF/non-IPF diagnosis using the two biopsy methods was 65.4% (κ = 0.57, 95% CI: 0.42-0.73) and 90.4% (47/52), respectively. Out of 38 (73.1%) cases diagnosed with high or definite confidence at TBLC-MDD, 29 had concordant SLB-MDD diagnoses (agreement: 76.3%, κ = 0.71, 95% CI: 0.55-0.87), and the agreement for IPF/non-IPF diagnoses was 97.4% (37/38). By adding the pathological diagnosis, the inter-observer agreement of clinical diagnosis improved from κ = 0.22 to κ = 0.42 for TBLC and from κ = 0.27 to κ = 0.38 for SLB, and the prevalence of high or definite diagnostic confidence improved from 23.0% to 73.0% and from 17.3% to 73.0%, respectively. Of all 383 TBLC performed during the same period, pneumothorax occurred in 5.0% of cases, and no severe bleeding, acute exacerbation of interstitial lung disease, or fatal event was observed.ConclusionsTBLC via a flexible bronchoscope under deep sedation is safely performed, and the TBLC-MDD diagnosis with a high or definite confidence level is concordant with the SLB-MDD diagnosis in the same patients.
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Project description:This paper analyzes firms’ episodes (spells) of high growth (HG) using a sample of Spanish manufacturing firms observed over two decades. The use of duration models allows us to investigate the following: (i) the probability of experiencing HG episodes, (ii) persistence in HG, and (iii) the determinants of the transitions in and out of the HG state and whether their impact varies over the business cycle. We find that about half of the firms experience at least one HG episode, but they seldom experience more than one. Moreover, high-growth status is rarely repeated due to high first-year selection. Yet, in subsequent years beyond the first one, the hazard rate from HG status falls substantially. These results suggest an “episodic” nature of HG and further allow us to identify two groups of firms characterized by the following: (i) (relatively) long HG spells and short no high-growth (NHG) spells and (ii) short HG spells and long NHG spells. In addition, some firm and market (demand) characteristics increase the probability of becoming an HG firm and enhancing HG persistence. Finally, during the downturn, the role of younger age and smaller size in explaining HG decreases. Supplementary Information The online version contains supplementary material available at 10.1007/s11187-020-00443-8.
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Project description:BackgroundAlthough transbronchial lung cryobiopsy (TBLC) is widely used in diagnostic algorithms for various interstitial lung diseases (ILDs), its real-world utility in the therapeutic decision-making strategy for ILD patients remains unclear, in particular, when judging the time to start antifibrotic agents.MethodsWe analyzed medical records of 40 consecutive patients with idiopathic or fibrotic hypersensitivity pneumonitis who underwent TBLC. A TBLC-based usual interstitial pneumonia (UIP) score was used to assess three morphologic descriptors: patchy fibrosis, fibroblastic foci, and honeycombing.ResultsIn our 40 patients with ILD, the most frequent radiological feature was indeterminate for UIP (45.0%). Final diagnosis included idiopathic pulmonary fibrosis (22.5%), fibrotic nonspecific interstitial pneumonia (5.0%), fibrotic hypersensitivity pneumonitis (35.0%), and unclassifiable ILD (37.5%). Linear mixed-effects analysis showed that declines in the slopes of %FVC and %DLCO in patients with TBLC-based UIP "Score ≥ 2" were significantly steeper than those of patients with "Score ≤ 1." During follow-up of patients with Score ≥ 2 (n = 24), more than half of them (n = 17) received an antifibrotic agent, with most patients (n = 13) receiving early administration of the antifibrotic agent within 6 months after the TBLC procedure.ConclusionsTBLC-based UIP Score ≥ 2 indicated the increased possibility of a progressive fibrosis course that may prove helpful in predicting progressive pulmonary fibrosis/progressive fibrosing ILD even if disease is temporarily stabilized due to anti-inflammatory agents. Patients may benefit from early introduction of antifibrotic agents by treating clinicians.
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Project description:ObjectiveTransbronchial lung cryobiopsy (TBLC) is a promising technique that can provide a histologic diagnosis in interstitial lung diseases (ILD) and is an alternative to surgical lung biopsy. The main concerns with the procedure are safety and diagnostic accuracy. The technique is applicable in patients unable to undergo surgical biopsy due to severe comorbidities or when patient transport to the operating room is dangerous. This study reports the initial experience with TBLC on a thoracic surgical service as a first attempt at diagnosis in patients with diffuse parenchymal lung diseases (DPLD).MethodsBetween May 2018 and July 2020, 32 patients underwent TBLC using bedside flexible bronchoscopy for suspected ILD on a thoracic surgical endoscopy service. Retrospective evaluation of the procedure details, complications, and diagnostic yield were analyzed and reported.ResultsA total of 89 pathological samples were obtained (mean 2.8 per patient). Pneumothorax and minor bleeding occurred in 25% and 16.7% of patients, respectively. Sixty-seven percent of complications occurred with use of the 2.4 mm cryoprobe (P = 0.036). Concordance between the histologic diagnosis and final clinical diagnosis was observed in 62.5% of patients and the pathology guided the final treatment in 71% (P = 0.027) with Kappa-concordance of 0.60 (P < 0.001).ConclusionsCryobiopsy is becoming part of the diagnostic evaluation in patients with indeterminate DPLD or hypoxemic respiratory failure. TBLC is easy to perform and has a favorable safety profile. Thoracic specialists should consider adding TBLC to their procedural armamentarium as a first option for patients with indeterminate PLD.
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Project description:BackgroundIn recent years, transbronchial cryobiopsy (TBCB) has come to be increasingly used in interventional pulmonology units as it obtains larger and better-quality samples than conventional transbronchial lung biopsy (TBLB) with forceps. No multicenter studies have been performed, however, that analyse and compare TBCB and TBLB safety and yield according to the interstitial lung disease (ILD) classification.ObjectivesWe compared the diagnostic yield and safety of TBCB with cryoprobe sampling versus conventional TBLB forceps sampling in the same patient.MethodProspective multicenter clinical study of patients with ILD indicated for lung biopsy. Airway management with orotracheal tube, laryngeal mask and rigid bronchoscope was according to the protocol of each centre. All procedures were performed using fluoroscopy and an occlusion balloon. TBLB was followed by TBCB. Complications were recorded after both TBLB and TBCB.ResultsIncluded were 124 patients from 10 hospitals. Airway management was orotracheal intubation in 74% of cases. Diagnostic yield according to multidisciplinary committee results for TBCB was 47.6% and for TBLB was 19.4% (p<0.0001). Diagnostic yield was higher for TBCB compared to TBLB for two groups: idiopathic interstitial pneumonias (IIPs) and ILD of known cause or association (OR 2.5; 95% CI: 1.4-4.2 and OR 5.8; 95% CI: 2.3-14.3, respectively). Grade 3 (moderate) bleeding after TBCB occurred in 6.5% of patients compared to 0.8% after conventional TBLB.ConclusionsDiagnostic yield for TBCB was higher than for TBLB, especially for two disease groups: IIPs and ILD of known cause or association. The increased risk of bleeding associated with TBCB confirms the need for safe airway management and prophylactic occlusion-balloon use.Trial registrationclinicaltrials.gov identifier: NCT02464592.
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Project description:A proportion of patients with interstitial lung diseases (ILDs), including the ILDs that are commonly associated with autoimmune diseases, develop a progressive fibrosing phenotype characterised by worsening of lung function, dyspnoea and quality of life, and early mortality. No drugs are approved for the treatment of ILDs other than idiopathic pulmonary fibrosis (IPF). At present, immunomodulatory medications are the mainstay of treatment for non-IPF ILDs. However, with the exception of systemic sclerosis-associated ILD, the evidence to suggest that immunosuppression may preserve lung function in patients with these ILDs comes only from retrospective, observational, or uncontrolled studies. In this article, we review the evidence for the treatments currently used to treat ILDs associated with autoimmune diseases and other ILDs and the ongoing trials of immunosuppressant and antifibrotic therapies in patients with these ILDs.Funding: Boehringer Ingelheim.
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Project description:Patients with certain types of fibrosing interstitial lung disease (ILD) are at risk of developing a progressive phenotype characterised by self-sustaining fibrosis, decline in lung function, worsening quality of life, and early mortality. It has been proposed that such progressive fibrosing ILDs, which show commonalities in clinical behaviour and in the pathogenetic mechanisms that drive progressive fibrosis, may be "lumped" together for the purposes of clinical research and, potentially, for treatment. At present, no drugs are approved for the treatment of ILDs other than nintedanib and pirfenidone for the treatment of idiopathic pulmonary fibrosis. For other progressive fibrosing ILDs, the mainstay of drug therapy is immunosuppression. However, it is postulated that, once the response to lung injury in fibrosing ILDs has reached the stage at which fibrosis has become progressive and self-sustaining, targeted antifibrotic therapy would be required to slow disease progression. Nintedanib, an intracellular inhibitor of tyrosine kinases, has shown antifibrotic, anti-inflammatory and vascular remodelling effects in several non-clinical models of fibrosis, irrespective of the trigger for the injury. Ongoing clinical trials will provide insight into the role of antifibrotic treatment with nintedanib or pirfenidone in the management of fibrosing ILDs with a progressive phenotype.
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Project description: Not available
| S-EPMC6812456 | biostudies-literature
Project description:BackgroundProposed criteria for progressive fibrosing interstitial lung disease (PF-ILD) have been linked to increased mortality risk, but lung function trajectory after satisfying individual criteria remains unknown. Because survival is rarely employed as the primary end-point in therapeutic trials, identifying PF-ILD criteria that best predict subsequent change in forced vital capacity (FVC) could improve clinical trial design.MethodsA retrospective, multicentre longitudinal cohort analysis was performed in consecutive patients with fibrotic connective tissue disease-associated ILD (CTD-ILD), chronic hypersensitivity pneumonitis and idiopathic interstitial pneumonia at three US centres (test cohort) and one UK centre (validation cohort). 1-year change in FVC after satisfying proposed PF-ILD criteria was estimated using joint modelling. Subgroup analyses were performed to determine whether results varied across key subgroups.Results1227 patients were included, with CTD-ILD predominating. Six out of nine PF-ILD criteria were associated with differential 1-year change in FVC, with radiological progression of fibrosis, alone and in combination with other features, associated with the largest subsequent decline in FVC. Findings varied significantly by ILD subtype, with CTD-ILD demonstrating little change in FVC after satisfying most PF-ILD criteria, while other ILDs showed significantly larger changes. Findings did not vary after stratification by radiological pattern or exposure to immunosuppressant therapy. Near-term change in FVC after satisfying proposed PF-ILD criteria was heterogeneous depending on the criterion assessed and was strongly influenced by ILD subtype.ConclusionsThese findings may inform future clinical trial design and suggest ILD subtype should be taken into consideration when applying PF-ILD criteria.
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