Prospective cohort of cryobiopsy in interstitial lung diseases: a single center experience.

RATIONALE: Transbronchial cryobiopsy has been increasingly used to diagnose interstitial lung diseases. However, there is uncertainty regarding its accuracy and risks, mainly due to a paucity of prospective or randomized trials comparing cryobiopsy to surgical biopsy. OBJECTIVES: To evaluate the diagnostic yield and complications of cryobiopsy in patients selected by multidisciplinary discussion. METHODS: This was a prospective cohort from 2017 to 2019. We included consecutive patients with suspected interstitial lung diseases being considered for lung biopsy presented at our multidisciplinary meeting. MEASUREMENTS AND MAIN RESULTS: Of 112 patients, we recommended no biopsy in 31, transbronchial forceps biopsy in 16, cryobiopsy in 54 and surgical biopsy in 11. By the end of the study, 34 patients had had cryobiopsy and 24 patients, surgical biopsy. Overall pathologic and multidisciplinary diagnostic yield of cryobiopsy was 47.1% and 61.8%, respectively. The yield increased over time for both pathologic (year 1: 28.6%, year 2: 54.5%, year 3: 66.7%, p = 0.161) and multidisciplinary (year 1: 50%, year 2: 63.6%, year 3: 77.8%, p = 0.412) diagnosis. Overall rate of grade 4 bleeding after cryobiopsy was 11.8%. Cryobiopsy required less chest tube placement (11.8% vs 100%, p < 0.001) and less hospitalizations compared to surgical biopsy (26.5% vs 95.7%, p < 0.001), but hospitalized patients had a longer median hospital stay (2 days vs 1 day, p = 0.004). CONCLUSIONS: Diagnostic yield of cryobiopsy increased over time but the overall grade 4 bleeding rate was 11.8%.

COVID19 Acute respiratory distress syndrome and extra-corporeal membrane oxygenation; A mere option or ultimate necessity.

Extracorporeal membrane oxygenation (ECMO) is considered a salvage therapy in patients with acute respiratory distress syndrome (ARDS) and refractory hypoxemia (hypoxemia persisting despite lung-protective ventilation). One aspect of ECMO is whether there would be an application of the technology related to the Coronavirus pandemic. The number of people diagnosed with Coronavirus disease (COVID19) has crossed the five million mark on 9 August 2020, with a case fatality rate of 5.2%. Due to this exponential increase in the number of coronavirus disease (COVID19) cases particularly the ones associated with ARDS, experts are evaluating the need for ECMO in intensive care units. Herein, we chronicle a review encompassing the available evidence on ECMO and its potential role in COVID19 ARDS, as we aim for optimal patient care with appropriate resource utilization and conservation.

A case of vaping-induced acute respiratory distress syndrome requiring extracorporeal life support.

INTRODUCTION: An upsurge of e-cigarette, or vaping, product use-associated lung injury has been reported in the United States. The potential role of extracorporeal life support in e-cigarette, or vaping, product use-associated lung injury merits consideration. CASE REPORT: We present a case of vaping-induced severe acute respiratory distress syndrome that was salvaged with extracorporeal life support and had excellent recovery. DISCUSSION: The mechanistic reasons for the sudden outbreak of e-cigarette, or vaping, product use-associated lung injury are under active investigation. A predominantly diffuse, bilateral pattern of lung injury has been reported, with some cases meeting the criteria for severe acute respiratory distress syndrome. To date, 68 deaths from e-cigarette, or vaping, product use-associated lung injury have been confirmed by the centers of disease control. However, resolution of lung injury has been reported in most cases, thereby justifying candidacy for extracorporeal life support, if required. CONCLUSION: Extracorporeal life support can be successfully utilized as a bridge to recovery in vaping-induced severe acute respiratory distress syndrome.

Bariatric surgery in patients with interstitial lung disease.

BACKGROUND: Perioperative pulmonary complications are frequent in patients with interstitial lung diseases (ILD). Limited literature exists regarding the safety of bariatric procedures in patients with ILD. This study aims to assess the safety, feasibility, and outcomes of patients with ILD who underwent bariatric surgery at our institution. METHODS: After IRB approval, all patients with preoperative diagnosis of ILD who had bariatric surgery at an academic center between 2004 and 2014 were retrospectively reviewed. RESULTS: A total of 25 patients with ILD underwent bariatric surgery: Roux-en-Y gastric bypass (n = 17, 68%), sleeve gastrectomy (n = 7, 28%), and adjustable gastric banding (n = 1, 4%). Twenty-one patients (84%) were females. The median age and preoperative body mass index (BMI) were 53 (IQR 42-58) years and 39 (IQR 37-44) kg/m2, respectively. The median operative time and length of stay was 137 (IQR 110-187) min and 3 (IQR 2-5) days, respectively. The 30-day complications were reported in four patients (16%) but there was no pulmonary complication or unplanned admission to the intensive care unit. At 1-year follow-up (85%), the median BMI and excess weight loss were 30 (IQR 25-36) kg/m2 and 67% (IQR 45-100), respectively. Compared to preoperative values, there was significant improvement in the pulmonary function test (PFT) variables at 1 year with respect to forced vital capacity (62% vs 74%; n = 13, p = 0.003), and diffusing capacity of the lungs for carbon monoxide (53% vs 66%; n = 10, p = 0.003). Six out of the seven potential lung transplant candidates became eligible for transplantation after weight loss, and one of them had successful lung transplant at 88 months after bariatric surgery. CONCLUSION: In our experience, bariatric patients with ILD achieved significant weight loss and improvement in PFT. Bariatric surgery in these higher risk ILD patients appears relatively safe with acceptable perioperative morbidity and improved candidacy for lung transplantation.

Danger-associated molecular patterns (DAMPs) in acute lung injury.

Danger-associated molecular patterns (DAMPs) are host-derived molecules that can function to regulate the activation of pathogen recognition receptors (PRRs). These molecules play a critical role in modulating the lung injury response. DAMPs originate from multiple sources, including injured and dying cells, the extracellular matrix, or exist as immunomodulatory proteins within the airspace and interstitium. DAMPs can function as either toll-like receptor (TLR) agonists or antagonists, and can modulate both TLR and nod-like receptor (NLR) signalling cascades. Collectively, this diverse group of molecules may represent important therapeutic targets in the prevention and/or treatment of acute lung injury (ALI) and its more severe form, acute respiratory distress syndrome (ARDS).

Smoking-Related Interstitial Fibrosis (SRIF) in Patients Presenting With Diffuse Parenchymal Lung Disease.

OBJECTIVES: To describe the clinical, radiologic, and pathologic findings in cases where smoking-related interstitial fibrosis (SRIF) was diagnosed in surgical lung biopsy specimens from patients with clinical and imaging features of diffuse parenchymal lung disease (DPLD). METHODS: Cases were included in this study if patients had clinical and imaging evidence of DPLD and surgical lung biopsy specimens revealed SRIF. A dedicated multidisciplinary conference was held to correlate clinical, radiologic, and pathologic findings. RESULTS: Six cases met inclusion criteria; all six (five women/one man, aged 42-57 years, mean age 47 years) were either current smokers (five of six) or ex-smokers (one of six) and were evaluated for respiratory symptoms and abnormal pulmonary function tests, most commonly reduced forced vital capacity (n = 3) and diffusing capacity for carbon monoxide (n = 6). The most common imaging abnormalities were bilateral ground-glass opacities, which correlated with histopathologic SRIF. Follow-up of up to 10 years showed stable or improved clinical symptoms, pulmonary function tests, and radiologic findings with smoking cessation (three patients) or a decrease in smoking (three patients). No specific treatments were given, and those treated with empiric corticosteroid tapers did not show discernible responses. CONCLUSIONS: SRIF can present as clinically meaningful diffuse parenchymal lung disease in relatively young heavy smokers, characterized by bilateral ground-glass opacities and a stable clinical course.

Challenges in the Diagnosis and Management of Patients with Fibrosing Interstitial Lung Disease.

Interstitial lung diseases (ILDs) are heterogeneous in their clinical presentation. Making a differential diagnosis of ILD requires a thorough medical history, clinical examination, serologies, high-resolution computed tomography (CT) scan, and, in some cases, bronchoalveolar lavage or surgical lung biopsy. Multidisciplinary discussion is recommended to improve diagnostic confidence. ILDs have a variable and unpredictable clinical course. Patients should be closely monitored to ensure that progression of ILD is detected promptly. This involves regular assessment of symptoms, lung function, and, where appropriate, high-resolution CT. Patients with some fibrosing ILDs may respond well to immunosuppressants, but even patients who respond well to immunosuppressants initially may later show deterioration despite appropriate management. The tyrosine kinase inhibitor nintedanib has been approved for the treatment of idiopathic pulmonary fibrosis, other chronic fibrosing ILDs with a progressive phenotype, and systemic sclerosis-associated ILD. The three case studies described in this article illustrate the challenges in the diagnosis and management of patients with fibrosing ILDs and the importance of taking a multidisciplinary and individualized approach to care, including regular monitoring and consideration of whether a patient's drug regimen needs to be changed when there is evidence of disease progression.

Overexpression of sICAM-1 in the alveolar epithelial space results in an exaggerated inflammatory response and early death in Gram negative pneumonia.

BACKGROUND: A sizeable body of data demonstrates that membrane ICAM-1 (mICAM-1) plays a significant role in host defense in a site-specific fashion. On the pulmonary vascular endothelium, mICAM-1 is necessary for normal leukocyte recruitment during acute inflammation. On alveolar epithelial cells (AECs), we have shown previously that the presence of normal mICAM-1 is essential for optimal alveolar macrophage (AM) function. We have also shown that ICAM-1 is present in the alveolar space as a soluble protein that is likely produced through cleavage of mICAM-1. Soluble intercellular adhesion molecule-1 (sICAM-1) is abundantly present in the alveolar lining fluid of the normal lung and could be generated by proteolytic cleavage of mICAM-1, which is highly expressed on type I AECs. Although a growing body of data suggesting that intravascular sICAM-1 has functional effects, little is known about sICAM-1 in the alveolus. We hypothesized that sICAM-1 in the alveolar space modulates the innate immune response and alters the response to pulmonary infection. METHODS: Using the surfactant protein C (SPC) promoter, we developed a transgenic mouse (SPC-sICAM-1) that constitutively overexpresses sICAM-1 in the distal lung, and compared the responses of wild-type and SPC-sICAM-1 mice following intranasal inoculation with K. pneumoniae. RESULTS: SPC-sICAM-1 mice demonstrated increased mortality and increased systemic dissemination of organisms compared with wild-type mice. We also found that inflammatory responses were significantly increased in SPC-sICAM-1 mice compared with wild-type mice but there were no difference in lung CFU between groups. CONCLUSIONS: We conclude that alveolar sICAM-1 modulates pulmonary inflammation. Manipulating ICAM-1 interactions therapeutically may modulate the host response to Gram negative pulmonary infections.

Idiopathic pulmonary fibrosis: exploring the clinical and economic implications of the evolving treatment landscape.

Idiopathic pulmonary fibrosis (IPF) is the most common idiopathic interstitial pneumonia, a form of interstitial lung disease characterized by abnormal wound healing in the lung that leads to progressive scarring and loss of lung function. Comorbidities are highly prevalent in IPF and often lead to further complications and worse outcomes. In fact, undetected and untreated comorbidities are independently associated with poor outcomes. IPF not only affects patient quality of life (QOL) but also requires significant cost for delivering care. Given the potential for rapid progression of IPF and the associated risk for mortality, early diagnosis is critical for retaining the highest lung function and QOL for as long as possible. Delayed diagnosis of IPF is associated with increased costs in terms of investigations performed, and delayed referral can result in lower survival rates independent of disease severity or associated prognostic factors. Significant progress has been made in understanding IPF pathogenesis, which has, in turn, led to the development of novel therapeutic options that improve outcomes, extend life, and minimize disease burden on patients' daily lives. For patients with IPF in the absence of underlying liver disease, pirfenidone and nintedanib are licensed for the treatment of IPF. Additionally, a number of investigational therapeutic options are currently in development. The extent of clinical effectiveness compared with the cost of therapy has led to a lack of consensus on the cost-vs-benefit analyses for the drugs.

Idiopathic pulmonary fibrosis: What primary care physicians need to know.

Idiopathic pulmonary fibrosis (IPF) is a specific type of fibrosing interstitial pneumonia of unknown cause. It is usually chronic and progressive, tends to affect mainly adults over age 60, has a predilection for men, and is often fatal. The condition is still underappreciated by pulmonologists and primary care physicians. This article attempts to close that information gap by reviewing the natural course of IPF and presenting an algorithmic approach to diagnosis and treatment based on evidence-based international guidelines. New treatment options are briefly discussed, to raise awareness of new medications that target pulmonary fibrosis.

Possible UIP pattern on high-resolution computed tomography is associated with better survival than definite UIP in IPF patients.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a progressive fibrosing lung disease of unknown etiology. Inter-society consensus guidelines on IPF diagnosis and management outline radiologic patterns including definite usual interstitial pneumonia (UIP), possible UIP, and inconsistent with UIP. We evaluate these diagnostic categories as prognostic markers among patients with IPF. METHODS: Included subjects had biopsy-proven UIP, a multidisciplinary team diagnosis of IPF, and a baseline high-resolution computed tomography (HRCT). Thoracic radiologists assigned the radiologic pattern and documented the presence and extent of specific radiologic findings. The outcome of interest was lung transplant-free survival. RESULTS: IPF patients with a possible UIP pattern on HRCT had significantly longer Kaplan-Meier event-free survival compared to those with definite UIP pattern (5.21 and 3.57 years, respectively, p = 0.002). In a multivariable Cox proportional hazards model adjusted for baseline age, gender, %-predicted FVC, and %-predicted DLCO via the GAP Stage, extent of fibrosis (via the traction bronchiectasis score) and ever-smoker status, possible UIP pattern on HRCT (versus definite UIP) was associated with reduced hazard of death or lung transplant (HR = 0.42, CI 95% 0.23-0.78, p = 0.006). CONCLUSIONS: Radiologic diagnosis categories outlined by inter-society consensus guidelines is a widely-reported and potentially useful prognostic marker in IPF patients, with possible UIP pattern on HRCT associated with a favorable prognosis compared to definite UIP pattern, after adjusting for relevant covariates.

Redundant and cooperative interactions between TLR5 and NLRC4 in protective lung mucosal immunity against Pseudomonas aeruginosa.

Flagellin is the major structural component of flagella expressed by Pseudomonas aeruginosa (PA) and other bacteria. This protein has been shown to activate the Toll-like receptor TLR5 and the Nod-like receptor Nlrc4/Ipaf, culminating in the expression of innate cytokines and antimicrobial molecules. In this study, we tested the hypothesis that TLR5 and Nlrc4 in combination are required for maximal protective lung innate mucosal immunity against PA. To test this hypothesis, we compared innate immune responses in wild-type (WT) C57B6 mice challenged with PA intratracheally to those observed in mice genetically deficient in TLR5 (TLR5(-/-)) or Nlrc4 (Nlrc4(-/-)) alone or in combination (TLR5/Nlrc4(-/-)). As compared to WT, TLR5(-/-) and Nlrc4(-/-) mice, we observed a significant increase in mortality in TLR5/Nlrc4(-/-) mice, which was associated with a >5,000-fold increase in lung PA colony-forming units and systemic bacterial dissemination. The increased mortality observed in double-deficient mice was not attributable to differences in lung leukocyte influx or lung injury responses. Levels of biologically active IL-1ß and IL-18 were reduced in the bronchoalveolar lavage fluid from PA-infected Nlrc4(-/-) and TLR5/Nlrc4(-/-) but not TLR5(-/-) mice, indicating the requirement for Nlrc4-dependent caspase-1 activation. Similarly, decreased production of biologically active IL-1ß and activation of caspase-1 was observed in PA-stimulated pulmonary macrophages isolated from Nlrc4(-/-) and TLR5/Nlrc4(-/-) but not TLR5(-/-) mice, whereas the expression of iNOS and the production of NO were significantly reduced in cells from double-mutant but not single-mutant mice. Collectively, our findings indicate that TLR5 and Nlrc4 have both unique and redundant roles in lung antibacterial mucosal immunity, and the absence of both pathogen recognition receptors results in an increase in susceptibility to invasive lung infection.