Ganesh Krishna

Transbronchial Cryobiopsy: A New Tool for Lung Biopsies

Background: Specimens from transbronchial lung biopsies lack sufficient quality due to crush artifact and are generally too small for diagnosis of diffuse lung diseases. Flexible cryoprobes have been shown to be useful in therapeutic bronchoscopy. We introduce a novel technique for obtaining lung biopsies bronchoscopically, using a flexible cryoprobe. Objectives: The purpose of this study was to show the feasibility of using a cryoprobe to obtain lung biopsies during flexible bronchoscopy. Methods: Forty-one patients with radiographic signs of diffuse lung disease were selected for transbronchial biopsy. During flexible bronchoscopy, conventional transbronchial biopsies using forceps were done first. Then a flexible cryoprobe was introduced into the selected bronchus under fluoroscopic guidance. Once brought into position, the probe was cooled and then retracted with the frozen lung tissue being attached on the probe’s tip. The tissue was processed for histology. After establishing a diagnosis, the specimen area was measured using a digital morphometry system. Results: We evaluated the biopsy samples of 41 patients. The mean specimen area was 5.82 mm2 (0.58–20.88 mm2) taken by forceps compared to 15.11 mm2 obtained using the cryoprobe (2.15–54.15 mm2, p < 0.01). Two patients had a pneumothorax which resolved with tube thoracostomy. Biopsy-associated bleeding did not require any intervention. Transbronchial cryobiopsy contributed in a substantial number of cases to a definitive diagnosis. Conclusions: Transbronchial cryobiopsy is a novel technique which allows to obtain large biopsy samples of lung parenchyma that exceed the size and quality of forceps biopsy samples. Prospective trials are needed to compare this technique with surgical lung biopsy for diagnosis of diffuse lung diseases.

Effect of Endobronchial Coils vs Usual Care on Exercise Tolerance in Patients With Severe Emphysema: The RENEW Randomized Clinical Trial

IMPORTANCE Preliminary clinical trials have demonstrated that endobronchial coils compress emphysematous lung tissue and may improve lung function, exercise tolerance, and symptoms in patients with emphysema and severe lung hyperinflation. OBJECTIVE To determine the effectiveness and safety of endobronchial coil treatment. DESIGN, SETTING, AND PARTICIPANTS Randomized clinical trial conducted among 315 patients with emphysema and severe air trapping recruited from 21 North American and 5 European sites from December 2012 through November 2015. INTERVENTIONS Participants were randomly assigned to continue usual care alone (guideline based, including pulmonary rehabilitation and bronchodilators; n = 157) vs usual care plus bilateral coil treatment (n = 158) involving 2 sequential procedures 4 months apart in which 10 to 14 coils were bronchoscopically placed in a single lobe of each lung. MAIN OUTCOMES AND MEASURES The primary effectiveness outcome was difference in absolute change in 6-minute-walk distance between baseline and 12 months (minimal clinically important difference [MCID], 25 m). Secondary end points included the difference between groups in 6-minute walk distance responder rate, absolute change in quality of life using the St Georges Respiratory Questionnaire (MCID, 4) and change in forced expiratory volume in the first second (FEV1; MCID, 10%). The primary safety analysis compared the proportion of participants experiencing at least 1 of 7 prespecified major complications. RESULTS Among 315 participants (mean age, 64 years; 52% women), 90% completed the 12-month follow-up. Median change in 6-minute walk distance at 12 months was 10.3 m with coil treatment vs -7.6 m with usual care, with a between-group difference of 14.6 m (Hodges-Lehmann 97.5% CI, 0.4 m to ∞; 1-sided P = .02). Improvement of at least 25 m occurred in 40.0% of patients in the coil group vs 26.9% with usual care (odds ratio, 1.8 [97.5% CI, 1.1 to ∞]; unadjusted between-group difference, 11.8% [97.5% CI, 1.0% to ∞]; 1-sided P = .01). The between-group difference in median change in FEV1 was 7.0% (97.5% CI, 3.4% to ∞; 1-sided P < .001), and the between-group St Georges Respiratory Questionnaire score improved -8.9 points (97.5% CI, -∞ to -6.3 points; 1-sided P < .001), each favoring the coil group. Major complications (including pneumonia requiring hospitalization and other potentially life-threatening or fatal events) occurred in 34.8% of coil participants vs 19.1% of usual care (P = .002). Other serious adverse events including pneumonia (20% coil vs 4.5% usual care) and pneumothorax (9.7% vs 0.6%, respectively) occurred more frequently in the coil group. CONCLUSIONS AND RELEVANCE Among patients with emphysema and severe hyperinflation treated for 12 months, the use of endobronchial coils compared with usual care resulted in an improvement in median exercise tolerance that was modest and of uncertain clinical importance, with a higher likelihood of major complications. Further follow-up is needed to assess long-term effects on health outcomes. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01608490.

PG490-88, a Derivative of Triptolide, Blocks Bleomycin-Induced Lung Fibrosis

In this study we evaluate the antifibrotic properties of PG-490-88, a water-soluble derivative of triptolide. Triptolide is an oxygenated diterpene that is derived from a traditional Chinese herb that has potent immunosuppressive and antitumor activity. We used the intratracheal bleomycin mouse model and found that PG490-88 inhibits fibrosis in the bleomycin group when given the same day or 5 days after bleomycin. PG490-88 also markedly reduced the number of myofibroblasts in the bleomycin treatment group. An enzyme-linked immunosorbent assay of transforming growth factor (TGF)-beta in the bronchoalveolar lavage fluid showed a significant decrease in TGF-beta in the PG490-88-treated groups compared to the bleomycin-treated group. Additionally, triptolide blocked bleomycin-induced increase in TGF-beta mRNA in cultured normal human lung fibroblasts. The efficacy of PG490-88 when administered late after bleomycin installation suggests a potential role in the treatment of idiopathic pulmonary fibrosis.

Nodular invasive tracheobronchitis due to Aspergillus in a patient with systemic lupus erythematosus

Nodular or pseudomembranous tracheobronchitis due to infection by Aspergillus species is an uncommon presentation of invasive aspergillosis. Most cases have been described in severely immunocompromised hosts. We describe the case of a 23-year-old woman, with recently diagnosed systemic lupus erythematosus, who developed worsening respiratory function. Bronchoscopy revealed rapid developmentand progression of multiple nodular plaques in her trachea and bronchi. Endobronchial biopsy demonstrated invasive fungal infection with tissue necrosis and the presence of hyphal elements consistent with aspergillosis. To the best of our knowledge, this is only the second report of fulminant invasive tracheobronchitis due to Aspergillus in a patient with an autoimmune disease.

Differential expression of monocyte/macrophage- selective markers in human idiopathic pulmonary fibrosis.

ABSTRACT Idiopathic interstitial pneumonias are a group of idiopathic interstitial lung diseases of which idiopathic pulmonary fibrosis (IPF) is the lesion of usual interstitial pneumonia. Although the pathogenic mechanisms remain incompletely understood, disease-specific changes in blood, a readily accessible biospecimen, have not been fully characterized. To identify biomarkers from blood and sera, the immune status of IPF patients and control subjects without structural lung disease was quantified by measuring cell surface markers, mRNA levels, and serum proteins. Statistically significant differences in cellular and molecular markers were observed between the 2 groups. The cytokine receptor IL-17RB was significantly higher in CD14+ peripheral blood mononuclear cells (PBMCs) from IPF patients, whereas expression of the chemokine receptor CXCR4 was lower. Gene expression analyses identified 18 differentially expressed genes out of 195 selected. Of these, EMR1, CCR3, UPAR, FCGR2A, OPN, CEACAM3, CD16a, CD18, CD11b, LTF, and LCN2 were up-regulated, whereas IL-17RB, IL-10, PDGFA, CD301/Clec10a, CD25/IL-2RA, IL-23p19, and IL-15 were down-regulated in IPF. Differentially regulated genes were in the functional areas of inflammation and cell signaling. Serum levels of UPAR and OPN were higher in IPF. These observations reveal significant differences in cell and molecular markers involved in monocyte/macrophage activation and migration, and suggest a role for IL-17RB in IPF.

Smoking cessation therapy with varenicline.

Smoking cessation is the only available intervention proven to halt progression of chronic obstructive pulmonary disease (COPD). The authors discuss the current existing treatment modalities and the role of a newly approved agent, varenicline, in promotion of smoking cessation. Varenicline is a novel agent that is a centrally acting partial nicotinic acetylcholine receptor agonist. It has both agonistic and antagonistic properties that together are believed to account for reduction of craving and withdrawal as well as blocking the rewarding effects of smoking. Its targeted mechanism of action, better efficacy and tolerability makes varenicline a useful therapeutic option for smoking cessation. In this article, we discuss presently available options for smoking cessation and review the literature on efficacy of varenicline.

Minimally invasive techniques for the diagnosis of peripheral pulmonary nodules

Purpose of review Evaluation and management of patients with pulmonary nodules continue to be a significant clinical challenge due to the possibility of malignancy. Recent findings With advances in technology, several minimally invasive diagnostic options are available for diagnosis of peripheral pulmonary lesions. Development and refinement of minimally invasive sampling techniques will aid in clinical decision making, as well as help advance scientific understanding of lung cancer growth and metastasis. Summary Although most surgical candidates should be referred promptly for resection, transthoracic or bronchoscopic biopsy may be particularly helpful when an infectious cause is suspected, when the patient is a marginal or poor candidate for surgery, or when a surgical candidate desires proof of malignancy before proceeding to surgery. Newer minimally invasive techniques should be rigorously evaluated for their role in the diagnostic algorithm of peripheral lung lesions.

Transbronchial Cryobiopsies for the Diagnosis of Diffuse Parenchymal Lung Diseases: Expert Statement from the Cryobiopsy Working Group on Safety and Utility and a Call for Standardization of the Procedure

Transbronchial cryobiopsies (TBCB) have recently been introduced as a promising and safer alternative to surgical lung biopsy in the diagnostic approach to diffuse parenchymal lung diseases (DPLD). Despite a substantial and expanding body of literature, the technique has not yet been standardized and its place in the diagnostic algorithm of DPLD remains to be defined. In part, this reflects concerns over the diagnostic yield and safety of the procedure, together with the rapid spread of the technique without competency and safety standards; furthermore, there is a substantial procedural variability among centers and interventional pulmonologists. We report this expert statement proposed during the third international conference on “Transbronchial Cryobiopsy in Diffuse Parenchymal Lung Disease” (Ravenna, October 27–28, 2016), which formulates evidence- and expert-based suggestions on the indications, contraindications, patient selection, and procedural aspects of the procedure. The following 5 domains were reviewed: (1) what is the role of TBCB in the diagnostic evaluation of DPLD: patient selection; (2) pathological considerations; (3) contraindications and safety considerations; (4) how should TBCB be performed and in what procedural environment; and (5) who should perform TBCB. Finally, the existence of white paper recommendations may also reassure local hospital credentialing committees tasked with endorsing an adoption of the technique.

Advances in the management of chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD), the fourth leading cause of death, seems to be increasing in worldwide prevalence, and carries with it a significant health and economic burden. Smoking cessation is the only available intervention proven to halt disease progression. The authors discuss the role of the newly approved agent, varenicline, in promotion of smoking cessation. The remainder of presently available therapies treat the symptoms of COPD, but do not impact progression of disease. As the understanding of the pathogenesis of COPD improves, new targets for therapies are emerging. Given the large number of potential targets and the results of recent studies, it seems unlikely that a single new agent will result in a cure. Rather, management of COPD should involve a multi-pronged approach including smoking cessation, bronchodilators, treatment of infection, and eventual targeting of inflammatory pathways and genetic predispositions. In this article, the authors discuss presently available therapies as well as agents under development.

The Diagnostic Yield of Navigational Bronchoscopy Performed with Propofol Deep Sedation

Objective. To describe the diagnostic yield of electromagnetic navigation bronchoscopy (ENB) utilizing propofol for procedural deep sedation. Methods. We conducted a structured retrospective analysis of the medical records of patients who underwent ENB with propofol for the evaluation of pulmonary nodules and masses. We analyzed the relationships between lesion size and location, variance (CT-to-body divergence), and positron emission tomography findings on diagnostic yield. Diagnoses were established by histopathological evaluation and clinical-radiographic followup. Results. 41 patients underwent ENB during the study period. The overall diagnostic yield was 89% (42 of 47 target lesions). Among the 42 positive specimens, the diagnoses were squamous cell carcinoma , adenocarcinoma , small cell carcinoma , adenocarcinoma in situ , coccidioidomycosis , and inflammatory processes . Average lesion size was  cm and variance  mm. The diagnostic yield was greater when the lesion size was >4 cm (100%) and when variance was ≤4 mm (91% versus 87%, ). Conclusion. The diagnostic yield of ENB utilizing propofol for procedural deep sedation at our center was excellent. ENB with deep sedation may result in superior diagnostic yield compared with ENB performed with moderate sedation.