Utility of a Molecular Classifier as a Complement to High-Resolution Computed Tomography to Identify Usual Interstitial Pneumonia.

Rationale: Usual interstitial pneumonia (UIP) is the defining morphology of idiopathic pulmonary fibrosis (IPF). Guidelines for IPF diagnosis conditionally recommend surgical lung biopsy for histopathology diagnosis of UIP when radiology and clinical context are not definitive. A "molecular diagnosis of UIP" in transbronchial lung biopsy, the Envisia Genomic Classifier, accurately predicted histopathologic UIP.Objectives: We evaluated the combined accuracy of the Envisia Genomic Classifier and local radiology in the detection of UIP pattern.Methods: Ninety-six patients who had diagnostic lung pathology as well as a transbronchial lung biopsy for molecular testing with Envisia Genomic Classifier were included in this analysis. The classifier results were scored against reference pathology. UIP identified on high-resolution computed tomography (HRCT) as documented by features in local radiologists' reports was compared with histopathology.Measurements and Main Results: In 96 patients, the Envisia Classifier achieved a specificity of 92.1% (confidence interval [CI],78.6-98.3%) and a sensitivity of 60.3% (CI, 46.6-73.0%) for histology-proven UIP pattern. Local radiologists identified UIP in 18 of 53 patients with UIP histopathology, with a sensitivity of 34.0% (CI, 21.5-48.3%) and a specificity of 96.9% (CI, 83.8-100%). In conjunction with HRCT patterns of UIP, the Envisia Classifier results identified 24 additional patients with UIP (sensitivity 79.2%; specificity 90.6%).Conclusions: In 96 patients with suspected interstitial lung disease, the Envisia Genomic Classifier identified UIP regardless of HRCT pattern. These results suggest that recognition of a UIP pattern by the Envisia Genomic Classifier combined with HRCT and clinical factors in a multidisciplinary discussion may assist clinicians in making an interstitial lung disease (especially IPF) diagnosis without the need for a surgical lung biopsy.

Disseminated Histoplasmosis in an Immunocompetent Patient After COVID-19 Pneumonia.

Disseminated histoplasmosis can occur in immunocompromised patients such as in HIV disease and patients with medication-induced immunosuppression. Most of these patients present with fever, weight loss, hepatosplenomegaly, lymphadenopathy, and pancytopenia. There are increasing reports of coronavirus disease 2019 (COVID-19) pneumonia associated with fungal infections including aspergillus and mucormycosis. It is not typical for immunocompetent patients to present with disseminated fungal disease. We herein report a case of a 50-year-old immunocompetent male with a recent recovery from COVID-19 pneumonia who presented with fever and pancytopenia. Chest computed tomography (CT) demonstrated new-onset right upper lobe lung mass, subcarinal lymphadenopathy, and splenomegaly. Mediastinal lymph nodes and bone marrow biopsies were performed, and the patient was diagnosed with disseminated histoplasmosis. The association between COVID-19 pneumonia and fungal infections is increasingly reported. Diagnosis requires a high index of suspicion, especially in immunocompetent patients.

Use of a molecular classifier to identify usual interstitial pneumonia in conventional transbronchial lung biopsy samples: a prospective validation study.

BACKGROUND: In the appropriate clinical setting, the diagnosis of idiopathic pulmonary fibrosis (IPF) requires a pattern of usual interstitial pneumonia to be present on high-resolution chest CT (HRCT) or surgical lung biopsy. A molecular usual interstitial pneumonia signature can be identified by a machine learning algorithm in less-invasive transbronchial lung biopsy samples. We report prospective findings for the clinical validity and utility of this molecular test. METHODS: We prospectively recruited 237 patients for this study from those enrolled in the Bronchial Sample Collection for a Novel Genomic Test (BRAVE) study in 29 US and European sites. Patients were undergoing evaluation for interstitial lung disease and had had samples obtained by clinically indicated surgical or transbronchial biopsy or cryobiopsy for pathology. Histopathological diagnoses were made by experienced pathologists. Available HRCT scans were reviewed centrally. Three to five transbronchial lung biopsy samples were collected from all patients specifically for this study, pooled by patient, and extracted for transcriptomic sequencing. After exclusions, diagnostic histopathology and RNA sequence data from 90 patients were used to train a machine learning algorithm (Envisia Genomic Classifier, Veracyte, San Francisco, CA, USA) to identify a usual interstitial pneumonia pattern. The primary study endpoint was validation of the classifier in 49 patients by comparison with diagnostic histopathology. To assess clinical utility, we compared the agreement and confidence level of diagnosis made by central multidisciplinary teams based on anonymised clinical information and radiology results plus either molecular classifier or histopathology results. FINDINGS: The classifier identified usual interstitial pneumonia in transbronchial lung biopsy samples from 49 patients with 88% specificity (95% CI 70-98) and 70% sensitivity (47-87). Among 42 of these patients who had possible or inconsistent usual interstitial pneumonia on HRCT, the classifier showed 81% positive predictive value (95% CI 54-96) for underlying biopsy-proven usual interstitial pneumonia. In the clinical utility analysis, we found 86% agreement (95% CI 78-92) between clinical diagnoses using classifier results and those using histopathology data. Diagnostic confidence was improved by the molecular classifier results compared with histopathology results in 18 with IPF diagnoses (proportion of diagnoses that were confident or provisional with high confidence 89% vs 56%, p=0·0339) and in all 48 patients with non-diagnostic pathology or non-classifiable fibrosis histopathology (63% vs 42%, p=0·0412). INTERPRETATION: The molecular test provided an objective method to aid clinicians and multidisciplinary teams in ascertaining a diagnosis of IPF, particularly for patients without a clear radiological diagnosis, in samples that can be obtained by a less invasive method. Further prospective clinical validation and utility studies are planned. FUNDING: Veracyte.

Indwelling Pleural Catheters for Nonmalignant Effusions: Evidence-Based Answers to Clinical Concerns.

Pleural effusions occur in 1.5 million patients yearly and are a common cause of dyspnea. For nonmalignant effusions, initial treatment is directed at the underlying cause, but when effusions become refractory to medical therapy, palliative options are limited. Tunneled pleural catheters (TPCs) are commonly used for palliation of malignant effusions, but many clinicians are reluctant to recommend these devices for palliation of nonmalignant effusions, citing concerns of infection, renal failure, electrolyte disturbances and protein-loss malnutrition. Based on the published experience to date, TPCs relieve dyspnea and can result in spontaneous pleurodesis in patients with nonmalignant effusions. The infection rate compares favorably to that for malignant effusions with possible increased risk in patients with hepatic hydrothorax and posttransplant patients. Renal failure, electrolyte disturbance and protein-loss malnutrition have not been observed. TPCs are a reasonable option in select patients to palliate nonmalignant effusions refractory to maximal medical therapy.

Linear EBUS-guided fiducial marker placement to guide radiotherapy for endobronchial, radiographically occult synchronous primary squamous cell carcinoma of the lung.

Radiation therapy has emerged as a useful alternative therapy for patients with early-stage, non-resectable lung cancer. In patients whose malignancies are difficult to localize on computed tomography imaging, such therapy becomes difficult. Fiducial markers are frequently placed in peripheral pulmonary lesions to assist radiation therapy. Although placement of markers under linear endobronchial ultrasonography within mediastinal and hilar lymph nodes has been reported, no strategy has been described to assist radiotherapy of purely endobronchial tumors. We present a case of bilateral, unresectable, radiographically occult endobronchial squamous cell carcinoma treated with radiotherapy guided by fiducial markers placed under linear endobronchial ultrasonographic guidance. The patient subsequently underwent intensity-modified radiation therapy to both lesions with pathologic complete response. Linear endobronchial ultrasound is a promising tool for placement of markers to guide radiation therapy of these difficult-to-treat lesions.

Atypical presentation of typical carcinoid.

Bronchial carcinoid tumours can present with symptoms of distal airway obstruction, local airway irritation or bleeding due to hypervascularity. Presentation with a spontaneous pneumothorax (SP) is rare. We present a case of typical endobronchial carcinoid tumour that presented with a SP. We explored the possible mechanisms of this rare presentation, especially the check-valve mechanism of airway obstruction, which was evident during the fiberoptic bronchoscopic examination.

Glomus tumor of the trachea.

Glomus tumors are uncommon soft tissue tumors that usually occur in the hands or feet but rarely have been described to appear in the tracheobronchial tree. Tracheal glomus tumors present with symptoms including cough, dyspnea, and wheezing that may be mistaken for other pulmonary disorders. Imaging and pulmonary function testing can detect tracheal obstruction, but pathology is necessary to differentiate glomus tumors from other airway tumors. On pathology, glomus tumors are made up of glomus cells, blood vessels, and smooth muscle and are classified based on the predominant cell type. The differential for this tumor includes carcinoid tumors, paragangliomas, and hemangiomas, and immunohistochemical stains can be used to obtain the correct diagnosis. The most common modality for treatment of these tracheal tumors has been surgical resection. However, there have been reported cases of successful removal with rigid or flexible bronchoscopy. We present a case of a tracheal glomus tumor that was successfully resected using electrocautery snare during flexible bronchoscopy. Our case adds to the evidence that flexible bronchoscopy is a safe, less invasive approach to management of tracheal glomus tumors in select patients.

Sequential comparison of tiotropium to high-dose ipratropium in patients with chronic obstructive pulmonary disease in a practice setting.

OBJECTIVE: To determine the effect of changing anticholinergic therapy in patients with COPD from ipratropium to tiotropium on pulmonary function. METHODS: We examined records of patients prescribed high-dose ipratropium, who were subsequently converted to tiotropium. Spirometric values were obtained within 2 days of the change in medication and after 56 to 224 days of the switch to tiotropium. RESULTS: 15 subjects were documented to have filled a prescription for ipratropium-containing medications the month prior to the change. Medication compliance over the 6 months prior to the switch in these patients was 72% +/- 31% (mean +/- SD) for ipratropium compared to 87% +/- 14% for tiotropium over the 6-month period after the switch (P = 0.1). FEV(1) improved from 1.12 +/- 0.39 L at baseline to 1.37 +/- 0.49 L after the change to tiotropium (P = 0.01). FVC also improved from 2.45 +/- 0.73 L at baseline to 2.72 +/- 0.69 L after the change (P = 0.04). Maximal voluntary ventilation was also increased from 39.67 +/- 10.7 L/min to 45.13 +/- 15.8 L/min (P = 0.045). CONCLUSIONS: We conclude that replacing high-dose ipratropium with tiotropium therapy significantly improves pulmonary function in a clinical setting.

Pulmonary manifestations of rheumatoid arthritis.

Rheumatoid arthritis (RA) is a systemic disease, characterized by symmetric joint involvement, but it can also affect other organ systems, including the lungs. The better-known pulmonary manifestations of RA are interstitial lung disease, rheumatoid nodules, and pleural effusions. Less common manifestations include bronchiolitis obliterans and crycoarytenoid arthritis. Management of these conditions involves, by and large, supportive pulmonary care and control of the underlying articular process. Other pulmonary manifestations in RA patients can ensue as a result of the treatments used for it, mainly methotrexate. This article discusses the most common pulmonary manifestations of RA and their treatment. A discussion about the increasing impact that cigarette smoking is having on RA is also provided.