Pathologic Criteria for the Diagnosis of Usual Interstitial Pneumonia vs Fibrotic Hypersensitivity Pneumonitis in Transbronchial Cryobiopsies.

Transbronchial cryobiopsy (TBCB) is increasingly used for the diagnosis of fibrosing interstitial pneumonias, but there are few detailed descriptions of the pathologic findings in such cases. It has been proposed that a combination of patchy fibrosis and fibroblast foci with an absence of alternative features is diagnostic of usual interstitial pneumonia (UIP; ie, idiopathic pulmonary fibrosis [IPF]) in TBCB. In this study, we reviewed 121 TBCB in which a diagnosis of fibrotic hypersensitivity pneumonitis (FHP; n = 83) or IPF (n = 38) was made by multidisciplinary discussion and evaluated a range of pathologic features. Patchy fibrosis was found in 65 of 83 (78%) biopsies from FHP and 32of 38 (84%) biopsies from UIP/IPF cases. Fibroblast foci were present in 47 of 83 (57%) FHP and 27 of 38 (71%) UIP/IPF cases. Fibroblast foci/patchy fibrosis combined did not favor either diagnosis. Architectural distortion was seen in 54 of 83 (65%) FHP and 32 of 38 (84%) UIP/IPF cases (odds ratio [OR] for FHP, 0.35; P = .036) and honeycombing in 18 of 83 (22%) and 17 of 38 (45%), respectively (OR, 0.37; P = .014). Airspace giant cells/granulomas were present in 13 of 83 (20%) FHP and 1 of 38 (2.6%) UIP/IPF cases (OR for FHP, 6.87; P = .068), and interstitial giant cells/granulomas in 20 of 83 (24%) FHP and 0 of 38 (0%) UIP/IPF (OR, 6.7 x 106; P = .000). We conclude that patchy fibrosis plus fibroblast foci can be found in TBCB from both FHP and UIP/IPF. The complete absence of architectural distortion/honeycombing favors a diagnosis of FHP, as does the presence of airspace or interstitial giant cells/granulomas, but these measures are insensitive, and many cases of FHP cannot be separated from UIP/IPF on TBCB.

Efficacy of the Spiration Valve System in Patients with Severe Heterogeneous Emphysema: A Systematic Review and Meta-Analysis.

BACKGROUND: Spiration Valve System (SVS) is an alternative for patients with severe heterogeneous emphysema; however, data about efficacy from randomized controlled trials (RCT) are unclear. OBJECTIVES: To explore both efficacy and safety of SVS in patients with severe emphysema and hyperinflation. METHODS: We included PubMed, EMBASE, Coch-rane database. All searches were performed until August 2019. Only RCTs were included for analysis. Risk of bias was assessed using Cochrane risk of bias tool. A meta-analysis evaluated change in forced expiratory volume in 1 s (FEV1), 6-min walking test (6MWT), residual volume, modified medical research council (mMRC) and Saint George respiratory questionnaire (SGRQ), all-cause mortality, risk of pneumothorax, and risk of acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Quality of the evidence was rated using GRADE approach. RESULTS: Four RCTs including 629 subjects were included. SVS showed an overall change of 0.03 L (-0.07 to 0.13, I2 = 90%) in the in FEV1 (L) and a 2.03% (-2.50 to 6.57, I2 = 96%) in the predicted FEV1 (%) compared to baseline; however, studies without collateral ventilation (CV) showed an improvement of 0.12 L (95% CI 0.09-0.015, I2 = 0%), This subgroup also reported better results in SGRQ -12.27 points (95% CI -15.84 to -8.70, I2 = 0%) and mMRC -0.54 (95% CI -0.74 to -0.33, I2 = 0%). We found no benefit in 6MWT mean difference = 4.56 m (95% CI -21.88 to 31.00, I2 = 73%). Relative risk of mortality was 2.54 (95% CI 0.81-7.96, I2 = 0%), for pneumothorax 3.3 (95% CI 0.61-18.12, I2 = 0%) and AECOPD 1.68 (95% CI 1.04-2.70, I2 = 0%). CONCLUSION: In patients with severe heterogeneous emphysema and hyperinflation without CV, SVS is an alternative that showed an improvement in pulmonary function, quality of life, and dyspnea score with an acceptable risk profile.

Single-center In-hospital Cardiac Arrest Outcomes.

BACKGROUND: This study was designed to evaluate the patient characteristics and outcomes of in-hospital cardiac arrest (IHCA). MATERIALS AND METHODS: We carried out a single-center, 5-year, retrospective chart review and analysis of resuscitation data for age, gender, body mass index (BMI), length of stay (LOS) until cardiac arrest, survival of initial IHCA, survival to hospital discharge, primary medical service, and determination of the etiology of cardiac arrest. RESULTS: A total of 500 cases occurred with a mean LOS of 8.5 days until the initial IHCA. Overall, 79.5% survived the initial IHCA and 32.4% survived to discharge. As LOS increased, there was an increase in the proportion of pulmonary and metabolic etiologies. Logistic regression analysis adjusting for BMI, gender, age, LOS, and primary medical service were on a surgical service significant for survival to discharge (p = 0.0007) and LOS <9 days significant for survival of IHCA (p = 0.018). CONCLUSION: There are a number of causes of IHCA, and the incidence of death and respiratory related IHCA etiologies increase with LOS. Length of stay carries the highest weight when predicting survival of IHCA. Also, there is a higher rate of survival to discharge when on a primary surgical service. HOW TO CITE THIS ARTICLE: Riley LE, Mehta HJ, Lascano J. Single-center In-hospital Cardiac Arrest Outcomes. Indian J Crit Care Med 2020;24(1):44-48.

Bronchoscopic Lung Volume Reduction with Endobronchial Zephyr Valves for Severe Emphysema: A Systematic Review and Meta-Analysis.

BACKGROUND: Endoscopic lung volume reduction using Zephyr® valves has been recently adopted as a treatment option for patients with severe emphysema without collateral ventilation (CV). OBJECTIVES: To assess the efficacy and safety of Zephyr valves in such a population. METHODS: Studies were identified from MEDLINE and EMBASE databases. All searches were current until June 2018. We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) evaluating the efficacy and safety of Zephyr. We defined as outcome: change in forced expiratory volume in 1 s (FEV1), in the 6-min walking test (6MWT), in the St George's Respiratory Questionnaire (SGRQ), and in residual volume (RV). Safety analysis included relative risk (RR) of pneumothorax. We assessed the quality of the evidence using GRADE. RESULTS: 7 RCTs reported on Zephyr valves and 5 RCTs included only patients without CV. Zephyr improved FEV1 with a mean difference (MD) of 17.36% (CI, 9.28-25.45, I2 = 78%). Subgroup analysis showed significant FEV1 improvement following Zephyr placement in patients with heterogeneous distribution: MD = 21.78% (CI, 8.70-34.86, I2 = 89%) and 16.27% (CI, 8.78-23.76, I2 = 0%) in patients with homogeneous emphysema. Studies with a follow-up of 3 months reported FEV1 MD = 17.19% (CI, 3.16-31.22, I2 = 89%) compared to studies with a follow-up of 6-12 months, which showed a consistent improvement of FEV1 MD = 17.90% (CI, 11.47-24.33, I2 = 0%). Zephyr also showed improvement of SGRQ, 6MWT, and RV. RR of pneumothorax was 6.32 (CI, 3.74-10.67, I2 = 0%). CONCLUSION: In this population, Zephyr valves provided significant and clinically meaningful short-term improvements in either homogeneous or heterogeneous emphysema without CV but with an increase in adverse events.

Association between inflammatory bowel disease and chronic obstructive pulmonary disease: a systematic review and meta-analysis.

INTRODUCTION: There is evidence of an association between inflammatory bowel disease (IBD) and lung conditions such as chronic obstructive pulmonary disease (COPD). This systematic review and meta-analysis explored the risk of new onset IBD in patients with COPD and new onset COPD in IBD patients. METHODS: We performed a systematic review of observational studies exploring the risk of both associations. Two independent reviewers explored the EMBASE, MEDLINE, LILACS and DOAJ databases, and the risk of bias was evaluated using the ROBBINS-I tool. Data from included studies was pooled in a random effect meta-analysis following a DerSimonian-Laird method. The quality of the evidence was ranked using GRADE criteria. RESULTS: Four studies including a pooled population of 1355 new cases were included. We found association between new onset IBD in COPD population. The risk of bias was low in most of them. Only one study reported tobacco exposure as a potential confounding factor. The pooled risk ratio (RR) for a new diagnosis of IBD in COPD patients was 2.02 (CI, 1.56 to 2.63), I2 = 72% (GRADE: low). The subgroup analyses for Crohn's disease and ulcerative colitis yielded RRs of 2.29 (CI, 1.51 to 3.48; I2 = 62%), and 1.79 (CI, 1.39 to 2.29; I2 = 19%.), respectively. DISCUSSION: According to our findings, the risk of new onset IBD was higher in populations with COPD compared to the general population without this condition. Based on our analysis, we suggest a potential association between IBD and COPD; however, further research exploring the potential effect of confounding variables, especially cigarette smoking, is still needed. REVIEW REGISTER: (PROSPERO: CRD42018096624).

[Airway tridimensional printing]. / Aplicaciones de la impresión 3D en la vía aérea central.

Tridimensional printing is becoming relevant in medicine, specially in surgical and interventional specialties. We review the technical aspects and clinical application of airway tridimensional printing. Using this technique, simulation models for bronchoscopy and models for diagnostic and therapeutic procedures such as stent design, tracheal reconstruction and airway models can be created.

Chronic obstructive pulmonary disease and lung cancer: inter-relationships.

PURPOSE OF REVIEW: Chronic obstructive pulmonary disease (COPD) is a well established risk factor for lung cancer. Newer studies reveal a myriad of other mechanisms, some proven and some putative, which may contribute to their association. RECENT FINDINGS: There is an ever-growing bundle of evidence that suggests a close association between persistent chronic inflammation and lung cancer. A few potential targets of genetic susceptibility locus for COPD and lung cancer have been suggested. Better characterization of immune dysregulation and identification of signaling pathways may assist the development of strategies to reduce risk of developing lung cancer in patients with COPD. Current lung cancer screening strategies may exclude some patients at high risk of having lung cancer. Prospective studies indicate that a screening criterion that includes variables reflecting the severity of COPD may increase the sensitivity of the screening program and reduce 'over-diagnosis bias' of indolent lung cancers. Examples of such variables include the emphysema score generated from computed tomography scans and diffusion capacity for carbon monoxide derived from lung function tests. SUMMARY: A better understanding of the inter-relationship between lung cancer pathogenesis and COPD has been described recently. Improving lung cancer screening strategies by incorporating markers of COPD severity has recently been proposed.

[Endoscopic lung volume reduction in advanced pulmonary emphysema: initial experience in Chile]. / Reducción de volumen pulmonar endoscópica en enfisema pulmonar avanzado: Casos clínicos.

Chronic obstructive pulmonary disease (COPD) has no curative treatment, and in moderate to advanced stages, functional parameters and quality of life are affected. Lung volume reduction improves respiratory parameters and quality of life of these patients. Endoscopic lung volume reduction is a minimally invasive procedure that uses endobronchial valves or coils. Valves are unidirectional, blocking the air from entering the target lobe during inspiration, allowing the exit of air and secretions during expiration. Complete fissure and absence of collateral ventilation are needed for an adequate functioning of endobronchial valves. Endobronchial coils cause mechanical retraction of the lung parenchyma. We report two patients who underwent endoscopic lung volume reduction by endobronchial valves. One patient was on continuous positive pressure non-invasive ventilation due to his severe emphysema.

Management of Intrapleural Sepsis with Once Daily Use of Tissue Plasminogen Activator and Deoxyribonuclease.

BACKGROUND: Pleural infection remains a significant cause of morbidity, mortality, prolonged hospital stay, and increased healthcare costs, despite advances in therapy. Twice daily intrapleural tissue plasminogen activator (tPA)/deoxyribonuclease (DNase) initiated at the time of diagnosis has been shown to significantly improve radiological outcomes and decrease the need for surgery. OBJECTIVES: To analyze our experience with once daily tPA/DNase for intrapleural sepsis. METHODS: Data derived from consecutive patients with empyema and complicated parapneumonic effusion who received once daily intrapleural tPA/DNase between January 2012 and August 2014 were reviewed. Measured outcomes included treatment success at 30 days, volume of pleural fluid drained, improvement in radiographic pleural opacity, length of hospital stay, need for surgery, and adverse events. RESULTS: 55 consecutive patients (33 male; mean age ± SD, 54.6 ± 16.1 years) were treated with once daily intrapleural tPA/DNase for 3 days. The majority of the patients (n = 51; 92.7%) were successfully managed without the need for surgical intervention. The mean change in pleural opacity measured on chest radiograph at day 7 was -28.8 ±17.6%. The median amount of fluid drained was 2,195 ml. No serious adverse events requiring discontinuation of intrapleural medications were observed. The most common complication was pain requiring escalating doses of analgesics (n = 8; 15%). Compliance with the protocol was excellent. CONCLUSION: Early administration of once daily intrapleural tPA/DNase for 3 days is safe, effective, and represents a viable option for the management of empyema and complicated parapneumonic effusion.

Indwelling pleural catheters for persistent pleural effusions secondary to post lung resection for malignancies.

Background: Malignant and nonmalignant pleural effusions (NMPEs) such as those due to hepatic hydrothorax have been successfully treated with an indwelling pleural catheter (IPC) with a low complication rate. There is no literature on the utility or safety of this treatment modality for NMPE post lung resection. We aimed to assess the utility of IPC for recurrent symptomatic NMPE secondary to post lung resection in lung cancer patients over a period of 4 years. Methods: Patients who underwent lobectomy or segmentectomy as part of the treatment plan for lung cancer between January 2019 and June 2022 were identified, these patients were screened for post-surgical pleural effusion. A total of 422 underwent lung resection, of which 12 had recurrent symptomatic pleural effusions requiring IPC placement and were selected for final analysis. The primary end points were improved symptomatology and successful pleurodesis. Results: Mean time to IPC placement was 78.4 days post-surgery. The mean length of IPC catheter was 77.7 days standard deviation (SD) 23.8. All 12 patients achieved spontaneous pleurodesis (SP), there was no second pleural intervention or re-accumulation of fluid on follow up imaging in any of the subjects after IPC removal. Two patients (16.7%) had skin infection related to catheter placement that was managed with oral antibiotics, there were no cases of pleural infections that required catheter removal. Conclusions: IPC is a safe and effective alternative in managing recurrent NMPE post lung cancer surgery with high rate of pleurodesis and acceptable complication rates.

Thoracoliths in Pleural Space Mimicking Lung Cancer: A Case Report.

Pulmonary nodules often present a diagnostic challenge due to their diverse etiology, ranging from benign to malignant conditions. We discuss the diagnostic journey of a 71-year-old female patient with a history of kidney stones, who was incidentally found to have a pleural-based pulmonary nodule during a CT urogram. Subsequent imaging showed nodule growth, prompting further investigations, including a PET/CT scan and CT-guided biopsy, which yielded inconclusive results. A multidisciplinary approach recommended surgical resection, revealing three mobile calcified-like nodules within the pleural space, later identified as hyalinized nodules. The absence of malignancy was reassuring. These benign, mobile pleural bodies, known as thoracoliths, are challenging to differentiate from pulmonary nodules. This case underscores the importance of considering rare benign entities in pulmonary nodule differentials and highlights the need for a multidisciplinary approach, surgical intervention, and open-mindedness in complex diagnostic scenarios.

Role of Transbronchial Lung Cryobiopsy in the Diagnosis of Interstitial Lung Disease: A Meta-analysis of 68 Studies and 6300 Patients.

BACKGROUND: Diagnosis of interstitial lung disease (ILD) is based on multidisciplinary team discussion (MDD) with the incorporation of clinical, radiographical, and histopathologic information if available. We aim to evaluate the diagnostic yield and safety outcomes of transbronchial lung cryobiopsy (TBLC) in the diagnosis of ILD. METHODS: We conducted a meta-analysis by comprehensive literature search to include all studies that evaluated the diagnostic yields and/or adverse events with TBLC in patients with ILD. We calculated the pooled event rates and their 95% confidence intervals (CIs) for the diagnostic yield by MDD, histopathologic diagnostic yield, and various clinical adverse events. RESULTS: We included 68 articles (44 full texts and 24 abstracts) totaling 6386 patients with a mean age of 60.7±14.1 years and 56% men. The overall diagnostic yield of TBLC to achieve a definite or high-confidence diagnosis based on MDD was 82.3% (95% CI: 78.9%-85.2%) and histopathologic diagnosis of 72.5% (95% CI: 67.7%-76.9%). The overall rate of pneumothorax was 9.6% (95% CI: 7.9%-11%), while the rate of pneumothorax requiring drainage by a thoracostomy tube was 5.3% (95% CI: 4.1%-6.9%). The rate of moderate bleeding was 11.7% (95% CI: 9.1%-14.9%), while the rate of severe bleeding was 1.9% (95% CI: 1.4%-2.6%). The risk of mortality attributed to the procedure was 0.9% (95% CI: 0.7%-1.3%). CONCLUSION: Among patients with undiagnosed or unclassified ILD requiring tissue biopsy for diagnosis, transbronchial cryobiopsy represents a reliable alternative to surgical lung biopsy with decreased incidence of various clinical adverse events.

Safety and Feasibility of Photodynamic Therapy for Ablation of Peripheral Lung Tumors.

BACKGROUND: Newer navigational bronchoscopy technologies render peripheral lung lesions accessible for biopsy and potential treatment. We investigated whether photodynamic therapy (PDT) delivered via navigational bronchoscopy is feasible and safe for ablation of peripheral lung tumors. METHODS: Two studies evaluated PDT in patients with solid peripheral lung tumors followed by clinical follow-up (nonresection study, N=5) or lobectomy (resection study, N=10). Porfimer sodium injection was administered 40 to 50 hours before navigational bronchoscopy. Lesion location was confirmed by radial probe endobronchial ultrasonography. An optical fiber diffuser was placed within or adjacent to the tumor under fluoroscopic guidance; laser light (630 nm wavelength) was applied at 200 J/cm of diffuser length for 500 seconds. Tumor response was assessed by modified Response Evaluation Criteria in Solid Tumors at 3 and 6 months postprocedure (nonresection study) and pathologically (resection study). RESULTS: There were no deaths, discontinuations for adverse events, or serious or grade ≥3 adverse events related to study treatments. Photosensitivity reactions occurred in 8 of 15 patients: 6 mild, 1 moderate, 1 severe (elevated porphyrins noted in blood after treatment). Among 5 patients with clinical follow-up, 1 had complete response, 3 had stable disease, and 1 had progressive disease at 6 months follow-up. Among 10 patients who underwent lobectomy, 1 had no evidence of tumor at resection (complete response), 3 had 40% to 50% tumor cell necrosis, 2 had 20% to 35%, and 4 had 5% to 10%. CONCLUSION: PDT for nonthermal ablation of peripheral lung tumors was feasible and safe in this small study. Further study is warranted to evaluate efficacy and corroborate the safety profile.

The Role of Surgery in Stage I Small Cell Lung Cancer: A National VA Database Analysis.

BACKGROUND: Historically, limited stage Small Cell Lung Cancer (SCLC) has been treated with concurrent chemoradiation (CRT). While current NCCN guidelines recommend consideration of lobectomy in node-negative cT1-T2 SCLC, data regarding the role of surgery in very limited SCLC is lacking. METHODS: Data from the National VA Cancer Cube were compiled. A total of 1,028 patients with pathologically confirmed stage I SCLC were studied. Only 661 patients that either received surgery or CRT were included. Interval-censored Weibull and Cox proportional hazard regression models were used to estimate median overall survival (OS) and hazard ratio (HR), respectively. Two survival curves were compared by a Wald test. Subset analysis was performed based on the location of the tumor in the upper vs. lower lobe as delineated by ICD-10 codes C34.1 and C34.3. RESULTS: Four-hundred and forty-six patients received concurrent CRT; while 223 underwent treatment that contained surgery (93 surgery only, 87 surgery/chemo, 39 surgery/chemo/radiation and 4 surgery/radiation). The median OS for the surgery-inclusive treatment was 3.87 years (95% CI 3.21-4.48) while median OS for the CRT cohort was 2.45 years (95% CI 2.17-2.74). HR of death for surgery-inclusive treatment when compared to CRT is 0.67 (95% CI 0.55-0.81; P < .001). Subset analysis based on the location of the tumor in both the upper or lower lobes showed improved survival with surgery as compared to CRT regardless of the location. HR for the upper lobe was 0.63 (95% CI 0.50-0.80; P < .001) and lower lobe 0.61 (95% CI 0.42-0.87; P = .006). Multivariable regression analysis accounting for age and ECOG-PS shows a HR 0.60 (95% CI 0.43-0.83; P = .002) favoring surgery. CONCLUSIONS: Surgery was used in less than a third of patients with stage I SCLC who received treatment. Surgery-inclusive multimodality treatment was associated with a longer overall survival as compared to chemoradiation, independent of age, performance status or tumor location. Our study suggests a more expansive role for surgery in stage I SCLC.

Survival Differences by Comorbidity Burden among Patients with Stage I/II Non-Small-Cell Lung Cancer after Thoracoscopic Resection.

We sought to compare overall survival (OS) by comorbidity burden among patients with stage I/II non-small cell lung cancer (NSCLC) who received thoracoscopic resection. Utilizing data from the National Cancer Database, we conducted a survival analysis among patients aged 50+ with stage I/II NSCLC who received thoracoscopic resection between 2010 and 2017. The comorbidity burden was measured by the Charlson comorbidity index (CCI, 0, 1, 2+). Multivariable Cox proportional hazard models were used to compare overall survival relative to the CCI (CCI of 0 as the referent). Subgroup analyses were conducted considering sex, age groups, days from diagnosis to surgery, facility type, laterality, and type of surgery. For this study, 61,760 patients were included, with a mean age of 69.1 years (SD: 8.5). Notably, 51.2% had a CCI of 0, 31.8% had a CCI of 1, and 17.0% had a CCI of 2+. Most participants were non-Hispanic White (87.5%), and 56.9% were female. We found that an increase in the CCI was associated with a higher risk of all-cause mortality (CCI 1 vs. 0 aHR: 1.24, 95% CI: 1.20-1.28; CCI 2+ vs. 0 aHR: 1.51, 95% CI: 1.45-1.57; p-trend < 0.01). Our subgroup analysis according to sex suggested that the association between CCI and risk of death was stronger in women.

A computational modeling approach for dosing endoscopic intratumoral chemotherapy for advanced non-small cell lung cancer.

We recently developed a computational model of cisplatin pharmacodynamics in an endobronchial lung tumor following ultrasound-guided transbronchial needle injection (EBUS-TBNI). The model suggests that it is more efficacious to apportion the cisplatin dose between injections at different sites rather than giving it all in a single central injection, but the model was calibrated only on blood cisplatin data from a single patient. Accordingly, we applied a modified version of our original model in a set of 32 patients undergoing EBUS-TBNI for non-small cell lung cancer (NSCLC). We used the model to predict clinical responses and compared them retrospectively to actual patient outcomes. The model correctly predicted the clinical response in 72% of cases, with 80% accuracy for adenocarcinomas and 62.5% accuracy for squamous-cell lung cancer. We also found a power-law relationship between tumor volume and the minimal dose needed to induce a response, with the power-law exponent depending on the number of injections administered. Our results suggest that current injection strategies may be significantly over- or under-dosing the agent depending on tumor size, and that computational modeling can be a useful planning tool for EBUS-TBNI of cisplatin in lung cancer.