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American Journal of Respiratory and... May 2022This American Thoracic Society, European Respiratory Society, Japanese Respiratory Society, and Asociación Latinoamericana de Tórax guideline updates prior idiopathic...
This American Thoracic Society, European Respiratory Society, Japanese Respiratory Society, and Asociación Latinoamericana de Tórax guideline updates prior idiopathic pulmonary fibrosis (IPF) guidelines and addresses the progression of pulmonary fibrosis in patients with interstitial lung diseases (ILDs) other than IPF. A committee was composed of multidisciplinary experts in ILD, methodologists, and patient representatives. ) Update of IPF: Radiological and histopathological criteria for IPF were updated by consensus. Questions about transbronchial lung cryobiopsy, genomic classifier testing, antacid medication, and antireflux surgery were informed by systematic reviews and answered with evidence-based recommendations using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. ) Progressive pulmonary fibrosis (PPF): PPF was defined, and then radiological and physiological criteria for PPF were determined by consensus. Questions about pirfenidone and nintedanib were informed by systematic reviews and answered with evidence-based recommendations using the GRADE approach. ) Update of IPF: A conditional recommendation was made to regard transbronchial lung cryobiopsy as an acceptable alternative to surgical lung biopsy in centers with appropriate expertise. No recommendation was made for or against genomic classifier testing. Conditional recommendations were made against antacid medication and antireflux surgery for the treatment of IPF. ) PPF: PPF was defined as at least two of three criteria (worsening symptoms, radiological progression, and physiological progression) occurring within the past year with no alternative explanation in a patient with an ILD other than IPF. A conditional recommendation was made for nintedanib, and additional research into pirfenidone was recommended. The conditional recommendations in this guideline are intended to provide the basis for rational, informed decisions by clinicians.
Topics: Antacids; Biopsy; Humans; Idiopathic Pulmonary Fibrosis; Lung; Lung Diseases, Interstitial; United States
PubMed: 35486072
DOI: 10.1164/rccm.202202-0399ST -
Modern Pathology : An Official Journal... Jan 2022The clinical and pathologic diagnosis of hypersensitivity pneumonitis has been confounded by conflicting definitions, with two recent guidelines suggesting that... (Review)
Review
The clinical and pathologic diagnosis of hypersensitivity pneumonitis has been confounded by conflicting definitions, with two recent guidelines suggesting that hypersensitivity pneumonitis simply be diagnosed as nonfibrotic or fibrotic. Nonfibrotic hypersensitivity pneumonitis is usually characterized by a bronchiolocentric chronic interstitial inflammatory infiltrate, frequently but by no means always with associated granulomas or giant cells. Fibrotic hypersensitivity pneumonitis may take the form of interstitial fibrosis confined to the peribronchiolar regions, or fibrotic nonspecific interstitial pneumonia, or a process similar to and sometimes indistinguishable from usual interstitial pneumonia/idiopathic interstitial fibrosis, but the exact pathologic features that favor a diagnosis of fibrotic hypersensitivity pneumonitis are disputed. Granulomas/giant cells are much less frequent in fibrotic compared to nonfibrotic hypersensitivity pneumonitis. Extensive peribronchiolar metaplasia, particularly peribronchiolar metaplasia affecting more than half the bronchioles, supports a diagnosis of fibrotic hypersensitivity pneumonitis over usual interstitial pneumonia, as does the presence of predominantly peribronchiolar disease with relative subpleural sparing. Clinical and CT features are crucial to the diagnosis of hypersensitivity pneumonitis: sparing of the lung bases, centrilobular nodules, air-trapping, or the triple density sign with fibrosis favor a diagnosis of fibrotic hypersensitivity pneumonitis. At this point there are no molecular tests that reliably separate fibrotic hypersensitivity pneumonitis from other forms of interstitial lung disease. Currently the separation of fibrotic hypersensitivity pneumonitis from usual interstitial pneumonia is crucial to treatment (immunosuppressives for the former, anti-fibrotics for the latter) but this approach is changing and all progressive fibrosing interstitial pneumonias will probably be treated with antifibrotics in the future.
Topics: Alveolitis, Extrinsic Allergic; Biopsy; Diagnosis, Differential; Humans; Idiopathic Pulmonary Fibrosis; Lung; Lung Diseases, Interstitial
PubMed: 34531525
DOI: 10.1038/s41379-021-00866-y -
Rhode Island Medical Journal (2013) Sep 2021Idiopathic pulmonary fibrosis (IPF) is the most common of the idiopathic interstitial pneumonias. Its signs and symptoms are relatively non-specific, and patients often... (Review)
Review
Idiopathic pulmonary fibrosis (IPF) is the most common of the idiopathic interstitial pneumonias. Its signs and symptoms are relatively non-specific, and patients often present with chronic cough, progressive dyspnea, resting or exertional hypoxemia, and inspiratory crackles on lung auscultation. Definitive diagnosis requires the exclusion of known causes of pulmonary fibrosis and identification of the usual interstitial pneumonia (UIP) pattern of disease either on high-resolution computed tomography (HRCT) scan of the chest or on surgical lung biopsy. Multidisciplinary discussion involving pulmonologists, radiologists, and pathologists with expertise in the diagnosis of IPF and other forms of interstitial lung disease is recommended and often required. Management focuses on anti-fibrotic therapy and early referral to lung transplant centers for those who are candidates. This review will discuss the current recommendations for the diagnosis, prognostication, and management of patients with IPF.
Topics: Biopsy; Diagnosis, Differential; Humans; Idiopathic Pulmonary Fibrosis; Lung; Lung Diseases, Interstitial; Tomography, X-Ray Computed
PubMed: 34437662
DOI: No ID Found -
Respiration; International Review of... 2020With the advent of lung cancer screening, and the increasingly frequent use of computed tomography (CT) scanning for investigating non-pulmonary pathology (for example... (Review)
Review
With the advent of lung cancer screening, and the increasingly frequent use of computed tomography (CT) scanning for investigating non-pulmonary pathology (for example CT coronary angiogram), the number of pulmonary nodules requiring further investigation has risen significantly. Most of these nodules are found in the lung periphery, which presents challenges to biopsy, and many centers rely on trans-thoracic needle biopsy performed under image guidance by radiologists. However, the desire to minimize complications is driving the development of increasingly accurate navigation bronchoscopy platforms, something that will be crucial in the new era of bronchoscopic therapeutics for lung cancer. This review describes these platforms, summarizes the current evidence for their use, and takes a look at future developments.
Topics: Bronchoscopy; Humans; Image-Guided Biopsy; Lung; Lung Neoplasms; Solitary Pulmonary Nodule; Surgery, Computer-Assisted; Surgical Navigation Systems; Tomography, X-Ray Computed
PubMed: 31600761
DOI: 10.1159/000503329 -
EBioMedicine Nov 2021Lung biopsy tissue samples can be used for infection detection and cancer diagnosis. Metagenomic next-generation sequencing (mNGS) has the potential to further improve...
BACKGROUND
Lung biopsy tissue samples can be used for infection detection and cancer diagnosis. Metagenomic next-generation sequencing (mNGS) has the potential to further improve diagnosis.
METHODS
From July 2018 to May 2020, lung biopsy samples of 133 patients with suspected pulmonary infection or abnormal imaging findings were collected and subjected to clinical microbiological testing, Illumina and Nanopore sequencing to identify pathogens. The neural networks were pretrained by extracting features of human reads from 2,095 metagenomic next-generation sequencing results, and the human reads of lung biopsy samples were entered into the validated pipeline to predict the risk of cancer.
FINDINGS
Based on the pathogen-cancer detection pipeline, the Illumina platform showed 77·6% sensitivity and 97·6% specificity compared to the composite reference standard for infection diagnosis. However, the Nanopore platform showed 34·7% sensitivity and 98·7% specificity. mNGS identified more fungi, which was confirmed by subsequent pathological examination. M. tuberculosis complex was weakly detected. For cancer detection, compared with histology, the Illumina platform showed 83·7% sensitivity and 97·6% specificity, diagnosing an additional 36 cancer patients, of whom half had abnormal imaging findings (pulmonary shadow, space-occupying lesions, or nodules).
INTERPRETATION
For the first time, we have established a pipeline to simultaneously detect pathogens and cancer based on Illumina sequencing of lung biopsy tissue. This pipeline efficiently diagnosed cancer in patients with abnormal imaging findings.
FUNDING
This work was supported by the National Key Research and Development Program of China and National Natural Science Foundation of China.
Topics: Adult; Aged; Biopsy; Disease Management; Disease Susceptibility; Female; Genomic Instability; High-Throughput Nucleotide Sequencing; Humans; Lung; Lung Diseases; Male; Metagenome; Metagenomics; Middle Aged; Neoplasms; Young Adult
PubMed: 34700283
DOI: 10.1016/j.ebiom.2021.103639 -
The European Respiratory Journal Nov 2022Circulating biomarkers for lung damage are lacking. Lung epithelium-specific DNA methylation patterns can potentially report the presence of lung-derived cell-free DNA...
BACKGROUND
Circulating biomarkers for lung damage are lacking. Lung epithelium-specific DNA methylation patterns can potentially report the presence of lung-derived cell-free DNA (cfDNA) in blood, as an indication of lung cell death.
METHODS
We sorted human lung alveolar and bronchial epithelial cells from surgical specimens, and obtained their methylomes using whole-genome bisulfite sequencing. We developed a PCR sequencing assay determining the methylation status of 17 loci with lung-specific methylation patterns, and used it to assess lung-derived cfDNA in the plasma of healthy volunteers and patients with lung disease.
RESULTS
Loci that are uniquely unmethylated in alveolar or bronchial epithelial cells are enriched for enhancers controlling lung-specific genes. Methylation markers extracted from these methylomes revealed that normal lung cell turnover probably releases cfDNA into the air spaces, rather than to blood. People with advanced lung cancer show a massive elevation of lung cfDNA concentration in blood. Among individuals undergoing bronchoscopy, lung-derived cfDNA is observed in the plasma of those later diagnosed with lung cancer, and to a lesser extent in those diagnosed with other lung diseases. Lung cfDNA is also elevated in patients with acute exacerbation of COPD compared with patients with stable disease, and is associated with future exacerbation and mortality in these patients.
CONCLUSIONS
Universal cfDNA methylation markers of normal lung epithelium allow for mutation-independent, sensitive and specific detection of lung-derived cfDNA, reporting on ongoing lung injury. Such markers can find broad utility in the study of normal and pathologic human lung dynamics.
Topics: Humans; DNA Methylation; Cell-Free Nucleic Acids; Liquid Biopsy; Biomarkers; Epithelium; Lung; Lung Neoplasms; Biomarkers, Tumor
PubMed: 35450968
DOI: 10.1183/13993003.03056-2021 -
Acta Cytologica 2023The International Academy of Cytology has joined with the International Agency for Research on Cancer (IARC) to bring together a group of experts in lung cytopathology... (Review)
Review
The International Academy of Cytology has joined with the International Agency for Research on Cancer (IARC) to bring together a group of experts in lung cytopathology to develop a WHO Reporting System for Lung Cytopathology (WHO System). This WHO System defines five categories for reporting lung cytopathology, that is, "Insufficient"/"Inadequate"/"Non-diagnostic," "Benign," "Atypical," "Suspicious for malignancy," and "Malignant," each with a clear descriptive term for the category, a definition, a risk of malignancy and a suggested management algorithm. The key diagnostic cytopathology features of each of the lesions within each category have been established by consensus and will be presented more fully in a subsequent IARC e-book and published hard cover book.The WHO System provides the best practice application of ancillary testing, including immunocytochemistry and molecular pathology, and provides a review to guide sampling and processing techniques to optimize the handling and preparation of the cytopathology sample emphasizing the cytomorphological differential diagnosis to aid low-resourced settings. The authors recognize that local medical and pathology resources will vary, particularly in low- and middle-income countries, and have developed the WHO System to make it applicable worldwide based on cytomorphology with options for further diagnostic management of the patient.The online WHO System provides a direct link to the WHO Tumour Classification for Thoracic Tumours 5th Edition. It will raise the profile and use of cytopathology by increasing awareness of its current role and its potential role in the era of personalized medicine based on molecular pathology utilizing "small biopsies." Ultimately, the System will improve patient care and outcomes.This System aims to improve and standardize the reporting of cytopathology, facilitate communication between cytopathologists and clinicians and improve patient care. The System is based on the current role of lung cytopathology and synthesizes the existing evidence while highlighting areas requiring further research and the future potential role of lung cytopathology.
Topics: Humans; Biopsy, Fine-Needle; Pathology, Clinical; Cytodiagnosis; Lung
PubMed: 36509066
DOI: 10.1159/000527580 -
The European Respiratory Journal Nov 2022In patients with interstitial lung diseases (ILD), histopathological input is often required to obtain a diagnosis. Surgical lung biopsy (SLB) is considered the...
BACKGROUND
In patients with interstitial lung diseases (ILD), histopathological input is often required to obtain a diagnosis. Surgical lung biopsy (SLB) is considered the reference standard, but many patients are clinically unfit to undergo this invasive procedure, and adverse events, length of hospitalisation and costs are considerable. This European Respiratory Society (ERS) guideline provides evidence-based clinical practice recommendations for the role of transbronchial lung cryobiopsy (TBLC) in obtaining tissue-based diagnosis in patients with undiagnosed ILD.
METHODS
The ERS Task Force consisted of clinical experts in the field of ILD and/or TBLC and methodological experts. Four PICO (Patient, Intervention, Comparator, Outcomes) questions and two narrative questions were formulated. Systematic literature searches were performed in MEDLINE and Embase (up to June 2021). GRADE (Grading, Recommendation, Assessment, Development and Evaluation) methodology was applied.
RESULTS
In patients with undiagnosed ILD and an indication to obtain histopathological data: 1) TBLC is suggested as a replacement test in patients considered eligible to undergo SLB, 2) TBLC is suggested in patients not considered eligible to undergo SLB, 3) SLB is suggested as an add-on test in patients with a non-informative TBLC, 4) no recommendation is made for or against a second TBLC in patients with a non-informative TBLC and 5) TBLC operators should undergo training, but no recommendation is made for the type of training required.
CONCLUSIONS
TBLC provides important diagnostic information in patients with undiagnosed ILD. Diagnostic yield is lower compared to SLB, at reduced serious adverse events and length of hospitalisation. Certainty of the evidence is mostly "very low".
Topics: Humans; Biopsy; Bronchoscopy; Cryosurgery; Lung; Lung Diseases, Interstitial
PubMed: 35710261
DOI: 10.1183/13993003.00425-2022 -
Pneumologie (Stuttgart, Germany) Jul 2020Cryosurgery has been successfully in bronchoscopy for several years. In addition to the local therapy of tumors and stenoses, cryo extraction enables the endobronchial...
Cryosurgery has been successfully in bronchoscopy for several years. In addition to the local therapy of tumors and stenoses, cryo extraction enables the endobronchial and transbronchial extraction of large, high-quality biopsies. This is with regard to the diagnosis of diffuse lung diseases and the molecular analysis of malignant lung tumors of outstanding importance. This article explains the method and implementation of transbronchial cryobiopsy.
Topics: Biopsy; Bronchi; Bronchoscopy; Cryosurgery; Humans; Lung; Lung Diseases; Pulmonary Medicine
PubMed: 32674192
DOI: 10.1055/a-0761-2551 -
Panminerva Medica Sep 2019Over the last decade transbronchial lung cryobiopsy (TBLC) has proven to be an "innovative application" of an "old procedure" for the histologic diagnosis of diffuse... (Review)
Review
Over the last decade transbronchial lung cryobiopsy (TBLC) has proven to be an "innovative application" of an "old procedure" for the histologic diagnosis of diffuse interstitial lung diseases (DILDs). Thus, the technique of TBL cryobiopsy is now adopted for diagnostic purposes, transbronchially in peripheral airways to sample lung parenchyma, whereas this same technique was traditionally employed in the past for therapeutic purposes, essentially for the management of malignant obstruction of central airways. When patients with interstitial lung diseases (ILDs) need histopathological data in their diagnostic pathway, this bioptic approach could be a valid alternative to surgical lung biopsy, that is still the gold standard at the moment. TBL cryobiopsy has a good safety profile, its sensitivity and specificity appear good overall in idiopathic pulmonary fibrosis. In the last ten years, many papers have been published about this procedure defining modalities by which cryobiopsy should be performed. These studies have shown that TBL cryobiopsy is feasible, it allows to obtain larger lung parenchymal specimens (3 times larger than "classic" transbronchial biopsies), characterized by unaltered and artefact-free morphology, and it represents a safe and poorly invasive diagnostic tool for the histologic diagnosis of ILDs. The technical aspects are really important, and they still need a complete standardization. TBL cryobiopsy should be part of an equipment of the modern interventional pulmonologist, who should know indications and contraindications of this methodic and the technical aspects of the procedure. This is a complex procedure requiring to be performed by endoscopists working in specialized centers with specific knowledge of DILDs, and a multidisciplinary approach, which represent pre-requisites for admission to training in this procedure.
Topics: Biopsy; Bronchi; Bronchoscopy; Clinical Competence; Cold Temperature; Cryosurgery; Endoscopy; Humans; Lung; Lung Diseases, Interstitial; Pulmonary Medicine; Sensitivity and Specificity
PubMed: 30394714
DOI: 10.23736/S0031-0808.18.03567-X