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1.
Transl Lung Cancer Res ; 13(6): 1346-1364, 2024 Jun 30.
Article in English | MEDLINE | ID: mdl-38973949

ABSTRACT

Background: Lung adenocarcinoma (LUAD) is among the most prevalent malignancies worldwide, with unfavorable treatment outcomes. Peptidyl-prolyl isomerase F (PPIF) is known to influence the malignancy traits of tumor progression by modulating the bioenergetics and mitochondrial permeability in cancer cells; however, its role in LUAD remains unclear. Our study seeks to investigate the clinical significance, tumor proliferation, and immune regulatory functions of PPIF in LUAD. Methods: The expression of PPIF in LUAD tissues and cells was assessed using bioinformatics analysis, immunohistochemistry (IHC), and Western blotting. Survival curve analysis was conducted to examine the prognostic association between PPIF expression and LUAD. The immunomodulatory role of PPIF in LUAD was assessed through the analysis of PPIF expression and immune cell infiltration. A series of gain- and loss-of-function experiments were conducted on PPIF to investigate its biological functions in LUAD both in vitro and in vivo. The mechanisms underlying PPIF's effects on LUAD were delineated through functional enrichment analysis and Western blotting assays. Results: PPIF exhibited overexpression in LUAD tissues compared to normal controls. Survival curve analysis revealed that patients with LUAD exhibiting higher PPIF expression demonstrated decreased overall survival and a shorter progression-free interval. PPIF was implicated in modulating immune cell infiltration, particularly in regulating the T helper 1-T helper 2 cell balance. Functionally, PPIF was discovered to promote tumor cell proliferation and advance cell-cycle progression. Furthermore, PPIF could impede mitophagy by targeting the FOXO3a/PINK1-Parkin signaling pathway. Conclusions: The findings of this study indicate that the prognosis-related gene PPIF may have a significant role in the regulation of LUAD cell proliferation, tumor-associated immune cell infiltration, and mitophagy, and thus PPIF may be a promising therapeutic target of LUAD.

2.
Expert Rev Respir Med ; 18(3-4): 175-188, 2024.
Article in English | MEDLINE | ID: mdl-38794918

ABSTRACT

INTRODUCTION: Lung nodules are commonly encountered in clinical practice. Technological advances in navigational bronchoscopy and imaging modalities have led to paradigm shift from nodule screening or follow-up to early lung cancer detection. This is due to improved nodule localization and biopsy confirmation with combined modalities of navigational platforms and imaging tools. To conduct this article, relevant literature was reviewed via PubMed from January 2014 until January 2024. AREAS COVERED: This article highlights the literature on different imaging modalities combined with commonly used navigational platforms for diagnosis of peripheral lung nodules. Current limitations and future perspectives of imaging modalities will be discussed. EXPERT OPINION: The development of navigational platforms improved localization of targets. However, published diagnostic yield remains lower compared to percutaneous-guided biopsy. The discordance between the actual location of lung nodule during the procedure and preprocedural CT chest is the main factor impacting accurate biopsies. The utilization of advanced imaging tools with navigation-based bronchoscopy has been shown to assist with localizing targets in real-time and improving biopsy success. However, it is important for interventional bronchoscopists to understand the strengths and limitations of these advanced imaging technologies.


Subject(s)
Bronchoscopy , Lung Neoplasms , Humans , Bronchoscopy/methods , Bronchoscopy/instrumentation , Lung Neoplasms/pathology , Lung Neoplasms/diagnostic imaging , Image-Guided Biopsy/methods , Solitary Pulmonary Nodule/diagnostic imaging , Solitary Pulmonary Nodule/pathology , Tomography, X-Ray Computed
3.
Respirology ; 29(4): 324-332, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38016646

ABSTRACT

BACKGROUND AND OBJECTIVE: Shape-sensing robotic-assisted bronchoscopy (ssRAB) has expanded as an important diagnostic tool for peripheral pulmonary nodules (PPNs), with diagnostic yields ranging from 60% to 88%. However, sampling and diagnosing PPN less than 2 cm in size has historically been challenging. Mobile cone-beam computed tomography (mCBCT) has been recently integrated into ssRAB to improve diagnostic accuracy, but its added value remains uncertain. We aim to describe the role of mCBCT and determine if it provides any diagnostic advantage. METHODS: A multicentre, retrospective study on the use of ssRAB and mCBCT in two tertiary care institutions: Mayo Clinic Florida and Massachusetts General Hospital. The primary outcome was diagnostic yield and sensitivity for malignancy of ssRAB complemented with mCBCT, compared to ssRAB with the standard 2D fluoroscopy. RESULTS: A total of 192 nodules were biopsied from 173 patients. mCBCT was used in 117 (60.9%) nodules. The overall diagnostic yield was 85.4%. Diagnostic yield between subgroups with and without mCBCT was 83.8% and 88% (p = 0.417), respectively. The mCBCT group had fewer solid nodules (65.8% vs. 81.3%, p = 0.020) and a higher number of ground-glass nodules (10.3% vs. 1.3%, p = 0.016). CONCLUSION: Overall, diagnostic yield between subgroups with and without mCBCT was similar. The complementary use of mCBCT to ssRAB allows proceduralists to target more complex and subsolid PPNs with a diagnostic yield comparable to simple solid PPNs while maintaining an excellent safety profile.


Subject(s)
Lung Neoplasms , Neoplasms , Robotic Surgical Procedures , Humans , Bronchoscopy/methods , Robotic Surgical Procedures/methods , Retrospective Studies , Cone-Beam Computed Tomography/methods , Lung Neoplasms/diagnostic imaging , Lung Neoplasms/pathology
4.
J Thorac Dis ; 15(7): 3557-3567, 2023 Jul 31.
Article in English | MEDLINE | ID: mdl-37559655

ABSTRACT

Background: An integrated classifier that utilizes plasma proteomic biomarker along with five clinical and imaging factors was previously shown to be potentially useful in lung nodule evaluation. This study evaluated the impact of the integrated proteomic classifier on management decisions in patients with a pretest probability of cancer (pCA) ≤50% in "real-world" clinical setting. Methods: Retrospective study examining patients with lung nodules who were evaluated using the integrated classifier as compared to standard clinical care during the same period, with at least 1-year follow-up. Results: A total of 995 patients were evaluated for lung nodules over 1 year following the implementation of the integrated classifier with 17.3% prevalence of lung cancer. 231 patients met the study eligibility criteria; 102 (44.2%) were tested with the integrated classifier, while 129 (55.8%) did not. The median number of chest imaging studies was 2 [interquartile range (IQR), 1-2] in the integrated classifier arm and 2 [IQR, 1-3] in the non-integrated classifier arm (P=0.09). The median outpatient clinic visit was 2.00 (IQR, 1.00-3.00) in the integrated classifier arm and 2.00 (IQR, 2.00-3.00) in the non-integrated classifier (P=0.004). Fewer invasive procedures were pursued in the integrated classifier arm as compared to non-integrated classifier respectively (26.5% vs. 79.1%, P<0.001). All patients in the integrated classifier arm with post-pCA (likely benign n=39) had designated benign diagnosis at 1-year follow-up. Conclusions: In patients with lung nodules with a pCA ≤50%, use of the integrated classifier was associated with fewer invasive procedures and clinic visits without misclassifying patients with likely benign lung nodules results at 1-year follow-up.

6.
Respirology ; 28(8): 722-743, 2023 08.
Article in English | MEDLINE | ID: mdl-37463832

ABSTRACT

BACKGROUND: Since their introduction, both linear and radial endobronchial ultrasound (EBUS) have become an integral component of the practice of Pulmonology and Thoracic Oncology. The quality of health care can be measured by comparing the performance of an individual or a health service with an ideal threshold or benchmark. The taskforce sought to evaluate quality indicators in EBUS bronchoscopy based on clinical relevance/importance and on the basis that observed significant variation in outcomes indicates potential for improvement in health care outcomes. METHODS: A comprehensive literature review informed the composition of a comprehensive list of candidate quality indicators in EBUS. A multiple-round modified Delphi consensus process was subsequently performed with the aim of reaching consensus over a final list of quality indicators and performance targets for these indicators. Standard reporting items were developed, with a strong preference for items where evidence demonstrates a relationship with quality indicator outcomes. RESULTS: Twelve quality Indicators are proposed, with performance targets supported by evidence from the literature. Standardized reporting items for both radial and linear EBUS are recommended, with evidence supporting their utility in assessing procedural outcomes presented. CONCLUSION: This statement is intended to provide a framework for individual proceduralists to assess the quality of EBUS they provide their patients through the identification of clinically relevant, feasible quality measures. Emphasis is placed on outcome measures, with a preference for consistent terminology to allow communication and benchmarking between centres.


Subject(s)
Pulmonary Medicine , Quality Indicators, Health Care , Humans , Bronchoscopy , Benchmarking , Endosonography
8.
J Bronchology Interv Pulmonol ; 30(1): 37-46, 2023 Jan 01.
Article in English | MEDLINE | ID: mdl-35318996

ABSTRACT

BACKGROUND: Careful selection of patients with expiratory central airway collapse (ECAC) that may benefit from tracheobronchoplasty (TBP) can be aided by a short-term airway stent evaluation. This can be performed with either silicone Y-stents (SYSs) or uncovered self-expanding metallic airway-stents (USEMAS). No direct comparison has been made between these 2 stent types. METHODS: This was a small retrospective review of consecutive patients that underwent a stent evaluation. A propensity score was used to match patients in the USEMAS and SYS groups. Outcomes included complications, changes in the health-related quality-of-life (HR-QoL), and changes in exercise capacity. Baseline measurements were compared with those obtained during stent evaluation and after TBP. RESULTS: Forty-two patients with severe ECAC underwent USEMAS placement, while 18 patients had an SYS placed. Propensity score matching resulted in 13 matched SYS and USEMAS pairs. The SYS group had an increased rate of mucus plugging (38.5% vs. 0%, P <0.047). Although not statically significant, a clinical improvement was observed in HR-QoL and exercise capacity in the USEMAS group during stent placement. In patients who underwent TBP, both USEMAS and SYS groups had a statistically significant change in the Modified Medical Research Council Dyspnea Scale during stent evaluation and after TBP. CONCLUSION: In patients with severe ECAC, short-term evaluation with airway stents appears to be safe and improves respiratory symptoms, HR-QoL, and exercise capacity. The use of USEMAS led to a lower complication rate, a greater improvement in HR-QoL and exercise capacity, and appeared to better predict how the patients would respond to TBP.


Subject(s)
Airway Obstruction , Quality of Life , Humans , Treatment Outcome , Stents , Retrospective Studies , Airway Obstruction/surgery
9.
J Thorac Cardiovasc Surg ; 165(2): 518-525, 2023 02.
Article in English | MEDLINE | ID: mdl-35764462

ABSTRACT

OBJECTIVES: This study examines the long-term anatomic and clinical effects of tracheobronchoplasty in severe excessive central airway collapse. METHODS: Included patients underwent tracheobronchoplasty for excessive central airway collapse (2002-2016). The cross-sectional area of main airways on dynamic airway computed tomography was measured before and after tracheobronchoplasty. Expiratory collapse was calculated as the difference between inspiratory and expiratory cross-sectional area divided by inspiratory cross-sectional area ×100. The primary outcome was improvement in the percentage of expiratory collapse in years 1, 2, and 5 post-tracheobronchoplasty. Secondary outcomes included mean response profile for the 6-minute walk test, Cough-Specific Quality of Life Questionnaire, Karnofsky Performance Status score, and St George Respiratory Questionnaire. Repeated-measures analysis of variance was used for statistical analyses. RESULTS: The cohort included 61 patients with complete radiological follow-up at years 1, 2, and 5 post-tracheobronchoplasty. A significant linear decrease in the percentage of expiratory collapsibility of the central airways after tracheobronchoplasty was present. Anatomic repair durability was preserved 5 years after tracheobronchoplasty, with decrease in percentage of expiratory airway collapse up to 40% and 30% at years 1 and 2, respectively. The St George Respiratory Questionnaire (74.7 vs 41.8%, P < .001) and Cough-Specific Quality of Life Questionnaire (78 vs 47, P < .001) demonstrated significant improvement at year 5 compared with baseline. Similar results were observed in the 6-minute walk test (1079 vs 1268 ft, P < .001) and Karnofsky score (57 vs 82, P < .001). CONCLUSIONS: Tracheobronchoplasty has durable effects on airway anatomy, functional status, and quality of life in carefully selected patients with severe excessive central airway collapse.


Subject(s)
Cough , Thoracic Surgical Procedures , Humans , Quality of Life , Exhalation/physiology
10.
Eur Respir J ; 61(4)2023 04.
Article in English | MEDLINE | ID: mdl-36549706

ABSTRACT

BACKGROUND: A genomic classifier for usual interstitial pneumonia (gUIP) has been shown to predict histological UIP with high specificity, increasing diagnostic confidence for idiopathic pulmonary fibrosis (IPF). Whether those with positive gUIP classification exhibit a progressive, IPF-like phenotype remains unknown. METHODS: A pooled, retrospective analysis of patients who underwent clinically indicated diagnostic bronchoscopy with gUIP testing at seven academic medical centres across the USA was performed. We assessed the association between gUIP classification and 18-month progression-free survival (PFS) using Cox proportional hazards regression. PFS was defined as the time from gUIP testing to death from any cause, lung transplant, ≥10% relative decline in forced vital capacity (FVC) or censoring at the time of last available FVC measure. Longitudinal change in FVC was then compared between gUIP classification groups using a joint regression model. RESULTS: Of 238 consecutive patients who underwent gUIP testing, 192 had available follow-up data and were included in the analysis, including 104 with positive gUIP classification and 88 with negative classification. In multivariable analysis, positive gUIP classification was associated with reduced PFS (hazard ratio 1.58, 95% CI 0.86-2.92; p=0.14), but this did not reach statistical significance. Mean annual change in FVC was -101.8 mL (95% CI -142.7- -60.9 mL; p<0.001) for those with positive gUIP classification and -73.2 mL (95% CI -115.2- -31.1 mL; p<0.001) for those with negative classification (difference 28.7 mL, 95% CI -83.2-25.9 mL; p=0.30). CONCLUSIONS: gUIP classification was not associated with differential rates of PFS or longitudinal FVC decline in a multicentre interstitial lung disease cohort undergoing bronchoscopy as part of the diagnostic evaluation.


Subject(s)
Idiopathic Pulmonary Fibrosis , Lung Diseases, Interstitial , Humans , Lung/pathology , Retrospective Studies , Idiopathic Pulmonary Fibrosis/diagnosis , Idiopathic Pulmonary Fibrosis/genetics , Lung Diseases, Interstitial/diagnosis , Lung Diseases, Interstitial/genetics , Vital Capacity , Genomics , Disease Progression
11.
J Thorac Dis ; 15(12): 7149-7154, 2023 Dec 30.
Article in English | MEDLINE | ID: mdl-38249911

ABSTRACT

Background: The migration of hook wire used for lung nodule localization to the pulmonary artery is an extremely rare complication. We report a case of migration of hook wire used for lung nodule localization to the main pulmonary artery and discuss the management. Case Description: The patient was a 50-year-old female with multiple pulmonary nodules, the largest of which was 7 mm and located in right lower lob. Since the size of the nodules were very small, three computed tomography (CT)-guided percutaneous hook wires were placed to localize the nodules prior to surgery. After entering the thorax, the wires were unable to be located in the right lower lobe and an intraoperative urgent chest CT demonstrated that the markers had migrated to the pulmonary artery. Therefore, the original surgical incision was extended and the superior tip subsegment of the pulmonary artery of the right lung was dissected open and the positioning needle was successfully removed. The patient was recovered without further complication and discharged 5 days later. Conclusions: When the exact location of a hook wire utilized for lung nodule localization cannot be determined, an exhaustive radiographic evaluation is required to determine the wire's specific location. If conditions permit, it is best to remove the hook wire directly using video-assisted thoracoscopic surgery (VATS). With careful perioperative assessment, surgeons can avoid additional complications and further surgery if they encounter a migrated nodule localization wire.

12.
Transl Lung Cancer Res ; 11(8): 1692-1701, 2022 Aug.
Article in English | MEDLINE | ID: mdl-36090647

ABSTRACT

Background: Self-expandable metallic (SEM) airway stents are an important approach to treating malignant central airway obstruction (CAO). Standard over-the-while (OTW) stent needs the guidance of a guide-wire. It should be implanted under flouroscopy or the guidance of bronchoscope visualization. In this study, we evaluated the operation time and safety between OTW stent and a novel through-the-scope (TTS) SEM airway stent. Methods: In this multi-center, randomized, parallel-group superiority study, malignant CAO patients were enrolled randomly assigned (2:1) to the TTS stent implantation group (TTS group) or the standard OTW stent group (OTW group) in six sites across China. The entire process of all surgical procedures was recorded by video. Primary endpoint was the operation time of the airway stent implantation and secondary endpoint was the success rate of the stent implantation as well as its efficacy and safety. Results: From May 15, 2017, to December 30, 2018, 148 patients were enrolled from the six sites. We analyzed 134 patients (including 91 patients from the TTS group and 43 patients from the OTW group) according to the per-protocol set. There were no significant differences in the ages, genders, underlying diseases, and stenosis sites between the two groups. The operation time in the TTS group was significantly shorter than that in the OTW group (104±68 vs. 252±111 seconds, P<0.001). Compared to the OTW group, the efficacy of stent implantation (97.80% vs. 90.70%, P=0.093) and rate of first-time successful stent implantation (78.02% vs. 74.42%, P=0.668) were higher in the TTS group, but did not reach statistically significance. The rates of granulation (28.57% vs. 41.86%, P=0.128) and restenosis (15.38% vs. 30.23%, P=0.064) in the TTS group were slightly lower as compared with the OTW group without achieving statistical significance. Conclusions: The TTS stent implantation procedure time was significantly shorter than that of the OTW airway stent with similar efficacy and complications, which might reduce the risk and flexibility of stent implantation. Trial Registration: Chinese Clinical Trial Registry ChiCTR-IOR-17011431.

13.
Chest ; 162(6): 1384-1392, 2022 Dec.
Article in English | MEDLINE | ID: mdl-35716828

ABSTRACT

BACKGROUND: Combination intrapleural fibrinolytic and enzyme therapy (IET) has been established as a therapeutic option in pleural infection. Despite demonstrated efficacy, studies specifically designed and adequately powered to address complications are sparse. The safety profile, the effects of concurrent therapeutic anticoagulation, and the nature and extent of nonbleeding complications remain poorly defined. RESEARCH QUESTION: What is the bleeding complication risk associated with IET use in pleural infection? STUDY DESIGN AND METHODS: This was a multicenter, retrospective observational study conducted in 24 centers across the United States and the United Kingdom. Protocolized data collection for 1,851 patients treated with at least one dose of combination IET for pleural infection between January 2012 and May 2019 was undertaken. The primary outcome was the overall incidence of pleural bleeding defined using pre hoc criteria. RESULTS: Overall, pleural bleeding occurred in 76 of 1,833 patients (4.1%; 95% CI, 3.0%-5.0%). Using a half-dose regimen (tissue plasminogen activator, 5 mg) did not change this risk significantly (6/172 [3.5%]; P = .68). Therapeutic anticoagulation alongside IET was associated with increased bleeding rates (19/197 [9.6%]) compared with temporarily withholding anticoagulation before administration of IET (3/118 [2.6%]; P = .017). As well as systemic anticoagulation, increasing RAPID score, elevated serum urea, and platelets of < 100 × 109/L were associated with a significant increase in bleeding risk. However, only RAPID score and use of systemic anticoagulation were independently predictive. Apart from pain, non-bleeding complications were rare. INTERPRETATION: IET use in pleural infection confers a low overall bleeding risk. Increased rates of pleural bleeding are associated with concurrent use of anticoagulation but can be mitigated by withholding anticoagulation before IET. Concomitant administration of IET and therapeutic anticoagulation should be avoided. Parameters related to higher IET-related bleeding have been identified that may lead to altered risk thresholds for treatment.


Subject(s)
Communicable Diseases , Empyema, Pleural , Pleural Diseases , Pleural Effusion , Humans , Tissue Plasminogen Activator/adverse effects , Fibrinolytic Agents/adverse effects , Retrospective Studies , Pleural Effusion/complications , Pleural Diseases/complications , Hemorrhage/chemically induced , Hemorrhage/epidemiology , Enzyme Therapy , Empyema, Pleural/drug therapy , Empyema, Pleural/epidemiology , Empyema, Pleural/complications
15.
Ann Am Thorac Soc ; 19(6): 1030-1039, 2022 06.
Article in English | MEDLINE | ID: mdl-35499847

ABSTRACT

Background: The American Thoracic Society, European Respiratory Society, Japanese Respiratory Society, and Asociación Latinoamericana del Tórax convened to update clinical practice guidelines for interstitial lung disease (ILD). Objective: To conduct a systematic review to evaluate existing ILD literature to determine whether patients with progressive pulmonary fibrosis (PPF) should be treated with the antifibrotic pirfenidone. Data Sources: A literature search was conducted across MEDLINE, EMBASE, and Cochrane databases through December 2020 for studies using pirfenidone to treat patients with PPF. Data Extraction: Mortality, disease progression, lung function, and adverse event data were extracted. Meta-analyses were performed when possible. The Grading of Recommendations, Assessment, Development and Evaluation Working Group approach was used to assess the quality of evidence. Synthesis: Two studies met inclusion criteria. Meta-analyses revealed that changes in forced vital capacity (FVC) percent predicted (mean difference [MD], 2.3%; 95% confidence interval [CI], 0.5-4.1%), the FVC in milliliters (MD, 100.0 ml; 95% CI, 98.1-101.9 ml), and the 6-minute-walk distance in meters (MD, 25.2 m; 95% CI, 8.3-42.1 m) all favored pirfenidone over placebo. The changes in the diffusing capacity of the lung for carbon monoxide (DLCO) in millimoles per kilopascal per minute (MD, 0.40 mmol/kPa/min; 95%, CI 0.10-0.70 mmol/kPa/min) and risk of DLCO declining more than 15% (relative risk [RR], 0.27; 95% CI, 0.08-0.95) also favored pirfenidone. The risks of gastrointestinal discomfort (RR, 1.83; 95% CI, 1.29-2.60) and photosensitivity (RR, 4.88; 95% CI, 1.09-21.83) were higher with pirfenidone. The quality of the evidence was low or very low according to the Grading of Recommendations, Assessment, Development and Evaluation criteria, depending on the outcome. Conclusions: Pirfenidone use in patients with PPF is associated with a statistically significant decrease in disease progression and with protection of lung function. However, there is very low certainty in the estimated effects because of limitations in the available evidence. Primary Source of Funding: Funded by the American Thoracic Society, European Respiratory Society, Japanese Respiratory Society, and Asociación Latinoamericana del Tórax.


Subject(s)
Lung Diseases, Interstitial , Pulmonary Fibrosis , Disease Progression , Humans , Pulmonary Fibrosis/drug therapy , Pyridones/therapeutic use
16.
Ann Am Thorac Soc ; 19(6): 1040-1049, 2022 06.
Article in English | MEDLINE | ID: mdl-35499854

ABSTRACT

Background: The American Thoracic Society, European Respiratory Society, Japanese Respiratory Society, and Asociación Latinoamericana del Tórax convened to update clinical practice guidelines for interstitial lung disease (ILD). Objective: To conduct a systematic review to evaluate existing ILD literature to determine whether patients with progressive pulmonary fibrosis (PPF) should be treated with the antifibrotic nintedanib. Data Sources: A literature search was conducted across MEDLINE, EMBASE, and Cochrane databases through December 2020 for studies using nintedanib to treat patients with PPF. Data Extraction: Mortality, disease progression, and adverse event data were extracted, and meta-analyses performed when possible. The Grading of Recommendations, Assessment, Development and Evaluation (GRADE) Working Group approach was used to assess the quality of evidence. Synthesis: Two relevant studies were selected. The annual decline in forced vital capacity was less in the nintedanib arm in the overall study population (mean difference [MD], 107 ml/yr; 95% confidence interval [CI], 65.4 to 148.5 ml/yr) and in the subgroups with usual interstitial pneumonia (UIP) pattern of pulmonary fibrosis (MD, 128.2 ml/yr; 95% CI, 70.8 to 185.6 ml/yr), non-UIP patterns of pulmonary fibrosis (MD, 75.3 ml/yr; 95% CI, 15.5 to 135.0 ml/yr), fibrotic connective tissue disease-related ILD (MD, 106.2 ml/yr; 95% CI, 10.6 to 201.9 ml/yr), fibrotic idiopathic nonspecific interstitial pneumonia (MD, 141.7 ml/yr; 95% CI, 46.0 to 237.4 ml/yr), and fibrotic occupational ILD (MD, 252.8 ml/yr; 95% CI, 79.2 to 426.5 ml/yr), but not fibrotic hypersensitivity pneumonitis (MD, 72.9 ml/yr; 95% CI, -8.9 to 154.7 ml/yr), fibrotic sarcoidosis (MD, -20.5 ml/yr; 95% CI, -337.1 to 296.1 ml/yr), or unclassified fibrotic ILD (MD, 68.5 ml/yr; 95% CI, -31.3 to 168.4 ml/yr) when compared with placebo. Gastrointestinal side effects were common. Quality of evidence for the outcomes ranged from very low to moderate GRADE. Conclusions: Nintedanib use in patients with PPF is associated with a statistically significant decrease in disease progression but increase in gastrointestinal side effects regardless of the radiographic pattern of pulmonary fibrosis. However, limitations in the available evidence lead to low certainty in these effect estimates and make definitive conclusions about the differential effects by subtype of ILD difficult to determine. Primary Source of Funding: Funded by the American Thoracic Society, European Respiratory Society, Japanese Respiratory Society, and Asociación Latinoamericana del Tórax.


Subject(s)
Idiopathic Pulmonary Fibrosis , Lung Diseases, Interstitial , Disease Progression , Humans , Idiopathic Pulmonary Fibrosis/drug therapy , Indoles/adverse effects , Lung Diseases, Interstitial/drug therapy
17.
Ann Am Thorac Soc ; 19(7): 1193-1202, 2022 07.
Article in English | MEDLINE | ID: mdl-35499855

ABSTRACT

Rationale: In 2018, a systematic review evaluating transbronchial lung cryobiopsy (TBLC) in patients with interstitial lung disease (ILD) was performed to inform American Thoracic Society, European Respiratory Society, Japanese Respiratory Society, and Asociación Latinoamericana del Tórax clinical practice guidelines on the diagnosis of idiopathic pulmonary fibrosis. Objectives: To perform a new systematic review to inform updated guidelines. Methods: Medline, Excerpta Medica Database, and the Cochrane Central Register of Controlled Trials (CCTR) were searched through June 2020. Studies that enrolled patients with ILD and reported the diagnostic yield or complication rates of TBLC were selected for inclusion. Data was extracted and then pooled across studies via meta-analysis. The quality of the evidence was appraised using the grading of recommendations, assessment, development, and evaluation approach. Results: Histopathologic diagnostic yield (number of procedures that yielded a histopathologic diagnosis divided by the total number of procedures performed) of TBLC was 80% (95% confidence interval [CI], 76-83%) in patients with ILD. TBLC was complicated by bleeding and pneumothorax in 30% (95% CI, 20-41%) and 8% (95% CI, 6-11%) of patients, respectively. Procedure-related mortality, severe bleeding, prolonged air leak, acute exacerbation, respiratory failure, and respiratory infection were rare. The quality of the evidence was very low owing to the uncontrolled study designs, lack of consecutive enrollment, and inconsistent results. Conclusions: Very low-quality evidence indicated that TBLC has a diagnostic yield of approximately 80% in patients with ILD, with manageable complications.


Subject(s)
Idiopathic Pulmonary Fibrosis , Lung Diseases, Interstitial , Biopsy/adverse effects , Biopsy/methods , Bronchoscopy/adverse effects , Bronchoscopy/methods , Hemorrhage/etiology , Humans , Idiopathic Pulmonary Fibrosis/diagnosis , Idiopathic Pulmonary Fibrosis/pathology , Lung/pathology , Lung Diseases, Interstitial/pathology
18.
Am J Respir Crit Care Med ; 205(9): e18-e47, 2022 05 01.
Article in English | MEDLINE | ID: mdl-35486072

ABSTRACT

Background: 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. Methods: A committee was composed of multidisciplinary experts in ILD, methodologists, and patient representatives. 1) 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. 2) 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. Results:1) 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. 2) 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. Conclusions: The conditional recommendations in this guideline are intended to provide the basis for rational, informed decisions by clinicians.


Subject(s)
Idiopathic Pulmonary Fibrosis , Lung Diseases, Interstitial , Antacids/therapeutic use , Biopsy , Humans , Idiopathic Pulmonary Fibrosis/drug therapy , Idiopathic Pulmonary Fibrosis/therapy , Lung/diagnostic imaging , Lung/pathology , Lung Diseases, Interstitial/pathology , United States
19.
Ann Am Thorac Soc ; 19(5): 833-844, 2022 05.
Article in English | MEDLINE | ID: mdl-35486080

ABSTRACT

Rationale: Idiopathic pulmonary fibrosis (IPF) is a fibrosing interstitial pneumonia with impaired survival. Previous guidelines recommend antacid medication to improve respiratory outcomes in patients with IPF. Objectives: This systematic review was undertaken during the development of an American Thoracic Society, European Respiratory Society, Japanese Respiratory Society, and Asociación Latinoamericana del Tórax guideline. The clinical question was, "Should patients with IPF who have documented abnormal gastroesophageal reflux (GER) with or without symptoms of GER disease 1) be treated with antacid medication or 2) undergo antireflux surgery to improve respiratory outcomes?" Methods: Medline, Embase, the Cochrane Central Register of Controlled Trials, and the gray literature were searched through June 30, 2020. Studies that enrolled patients with IPF and 1) compared antacid medication to placebo or no medication or 2) compared antireflux surgery to no surgery were selected. Meta-analyses were performed when possible. Outcomes included disease progression, mortality, exacerbations, hospitalizations, lung function, respiratory symptoms, GER severity, and adverse effects/complications. Results: For antacid medication, when two studies were aggregated, there was no statistically significant effect on disease progression, defined as a 10% or more decline in FVC, more than 50-m decline in 6-minute walking distance, or death (risk ratio [RR], 0.88; 95% confidence interval [CI], 0.76-1.03). A separate study that could not be included in the meta-analysis found no statistically significant effect on disease progression when defined as a 5% or more decline in FVC or death (RR, 1.10; 95% CI, 1.00-1.21) and an increase in disease progression when defined as a 10% or more decline in FVC or death (RR, 1.28; 95% CI, 1.08-1.51). For antireflux surgery, there was also no statistically significant effect on disease progression (RR, 0.29; 95% CI, 0.06-1.26). Neither antacid medications nor antireflux surgery was associated with improvements in the other outcomes. Conclusions: There is insufficient evidence to conclude that antacid medication or antireflux surgery improves respiratory outcomes in patients with IPF, most of whom had not had abnormal GER confirmed. Well-designed and adequately powered prospective studies with objective evaluation for GER are critical to elucidate the role of antacid medication and antireflux surgery for respiratory outcomes in patients with IPF.


Subject(s)
Gastroesophageal Reflux , Idiopathic Pulmonary Fibrosis , Antacids/therapeutic use , Disease Progression , Gastroesophageal Reflux/complications , Gastroesophageal Reflux/drug therapy , Gastroesophageal Reflux/surgery , Humans , Idiopathic Pulmonary Fibrosis/complications , Idiopathic Pulmonary Fibrosis/drug therapy , Idiopathic Pulmonary Fibrosis/surgery , Prospective Studies
20.
Transl Lung Cancer Res ; 11(3): 393-403, 2022 Mar.
Article in English | MEDLINE | ID: mdl-35399565

ABSTRACT

Background: Percutaneous transthoracic lung biopsy is customarily conducted under computed tomography (CT) guidance, which primarily depends on the conductors' experience and inevitably contributes to long procedural duration and radiation exposure. Novel technique facilitating lung biopsy is currently demanded. Methods: Based on the reconstructed anatomical information of CT scans, a three-dimensionally printed navigational template was customized to guide fine-needle aspiration (FNA). The needle insertion site and angle could be indicated by the template after proper placement according to the reference landmarks. From June 2020 to August 2020, patients with peripheral indeterminate lung lesions ≥30 mm in diameter were enrolled in a pilot trial. Cases were considered successful when the virtual line indicated by the template in the first CT scan was pointing at the target, and the rate of success was recorded. The insertion deviation, procedural duration, radiation exposure, biopsy-related complications, and diagnostic yield were documented as well. Results: A total of 20 patients consented to participate, and 2 withdrew. The remaining 18 participants consisting of 11 men and 7 women with a median age of 63 [inter-quartile range (IQR), 50-68] years and a median body mass index (BMI) of 23.5 (IQR, 20.8-25.8) kg/m2 received template-guided FNA. The median nodule size of the patients was 41.2 (IQR, 36.2-51.9) mm and 17 lesions were successfully targeted (success rate, 94.4%). One lesion was not reached through the designed trajectory due to an unpredictable alteration of the lesion's location resulting from pleural effusion. The median deviation between the actual position of the needle tip and the designed route was 9.4 (IQR, 6.8-11.7) mm. The median procedural duration was 10.7 (IQR, 9.7-11.8) min, and the median radiation exposure was 220.9 (IQR, 198.6-249.5) mGy×cm. No major biopsy-related complication was encountered. Definitive diagnosis of malignancy was reached in 13 of the 17 (76.5%) participants. Conclusions: The feasibility and safety of navigational template-guided FNA were preliminarily validated in lung biopsy cohort. Nonetheless, patients with pleural effusion were not recommended to undergo FNA guided by such technique. Trial Registration: This study was registered with ClinicalTrials.gov (identifier: NCT03325907).

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