Diffuse Alveolar Hemorrhage Following Pirfenidone Initiation.

INTRODUCTION: Diffuse alveolar hemorrhage (DAH) is bleeding into the alveolar space of the lungs. Pirfenidone is an antifibrotic agent that is approved for the treatment of idiopathic pulmonary fibrosis (IPF). The most commonly reported side effects include gastrointestinal and skin-related events. We present 3 cases of hemoptysis and DAH among patients on pirfenidone therapy for IPF. CASE SUMMARIES: An 88-year-old female, a 75-year-old male, and a 73-year-old male all with IPF on pirfenidone presented with hemoptysis and chest computed tomography (CT) findings of usual interstitial pneumonia (UIP) with superimposed opacities. In 2 patients, DAH was confirmed with bronchoscopy. Corticosteroids were initiated and pirfenidone discontinued in all patients, and 2 patients improved while the third continued to deteriorate. Nintedanib was initiated in the remaining 2 patients at follow-up visit with no further issues. DISCUSSION: IPF is a chronic, progressive, fibrotic interstitial lung disease (ILD) which appears to be increasing in the United States and has a relatively short survival. Nintedanib and pirfenidone were the first Food and Drug Administration (FDA)-approved agents for the treatment of IPF in October 2014. We present 3 cases of DAH in patients with IPF receiving pirfenidone. Symptoms occurred within 2 months of pirfenidone initiation and resolved with discontinuation of pirfenidone and initiation of systemic corticosteroids in 2 patients; however, one case was complicated by concomitant discontinuation of aspirin. The mechanism by which DAH occurred in our patients remains unclear. CONCLUSION: We report the first cases of possible pirfenidone-induced DAH. Further studies are warranted to explore this reaction, but prescribers should be cognizant of this potential issue when choosing to prescribe pirfenidone.

The Impact of Gravity vs Suction-driven Therapeutic Thoracentesis on Pressure-related Complications: The GRAVITAS Multicenter Randomized Controlled Trial.

BACKGROUND: Thoracentesis can be accomplished by active aspiration or drainage with gravity. This trial investigated whether gravity drainage could protect against negative pressure-related complications such as chest discomfort, re-expansion pulmonary edema, or pneumothorax compared with active aspiration. METHODS: This prospective, multicenter, single-blind, randomized controlled trial allocated patients with large free-flowing effusions estimated ≥ 500 mL 1:1 to undergo active aspiration or gravity drainage. Patients rated chest discomfort on 100-mm visual analog scales prior to, during, and following drainage. Thoracentesis was halted at complete evacuation or for persistent chest discomfort, intractable cough, or other complication. The primary outcome was overall procedural chest discomfort scored 5 min following the procedure. Secondary outcomes included measures of discomfort and breathlessness through 48 h postprocedure. RESULTS: A total of 142 patients were randomized to undergo treatment, with 140 in the final analysis. Groups did not differ for the primary outcome (mean visual analog scale score difference, 5.3 mm; 95% CI, -2.4 to 13.0; P = .17). Secondary outcomes of discomfort and dyspnea did not differ between groups. Comparable volumes were drained in both groups, but the procedure duration was significantly longer in the gravity arm (mean difference, 7.4 min; 95% CI, 10.2 to 4.6; P < .001). There were no serious complications. CONCLUSIONS: Thoracentesis via active aspiration and gravity drainage are both safe and result in comparable levels of procedural comfort and dyspnea improvement. Active aspiration requires less total procedural time. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT03591952; URL: www.clinicaltrials.gov.

Waste not, want not: diagnostic material found in suction syringe aspirate during endobronchial ultrasound guided transbronchial needle aspiration.

BACKGROUND: Endobronchial ultrasound transbronchial needle aspiration (EBUS-TBNA) is a frequently performed procedure. Suction is utilized during this procedure and may occasionally result in the collection of aspirated material, the diagnostic utility of which is uncertain. This study aims to determine the contents of the suction syringe aspirate and its diagnostic value. METHODS: The suction syringe aspirate was pooled in a container and sent for analysis. We retrospectively reviewed the cytological outcomes of these specimens in comparison to the diagnosis determined by EBUS-TBNA between 2015-2018. The primary outcome was the percent agreement between the diagnostic material found in the suction syringe aspirate, and the final diagnosis established by EBUS-TBNA. RESULTS: Forty-four patients were included. Percent agreement was calculated as the percent in which the suction syringe aspirate diagnosis agreed with the EBUS-TBNA diagnosis. The percent agreement of any diagnosis was 90.9% (95% CI: 78.7-97.2%). Two of the 44 diagnoses (4.5%) were established based solely on the suction syringe aspirate, both cases of granulomatous inflammation. CONCLUSIONS: Our results suggest that material collected in the suction syringe has a very high percent agreement with the final diagnosis established by EBUS-TBNA. Furthermore, the suction syringe aspirate may represent the sole diagnostic material in nearly 5% of cases. Given the additional diagnostic material in the suction syringe aspirate, it is reasonable to pool the aspirate with the primary specimen in an effort to enrich the overall diagnostic specimen. This practice may improve the likelihood that the specimen will be sufficient for additional molecular analysis, although further study is necessary. Care must be taken when more than one needle is involved to ensure that a new suction syringe is also used to avoid inadvertent upstaging by specimen contamination.

Esophagorespiratory Fistulas: Survival and Outcomes of Treatment.

GOAL: The purpose of this study was to characterize outcomes of esophagorespiratory fistulas (ERF) by etiology and initial treatment strategy. BACKGROUND: ERF is a morbid condition for which optimal treatment strategies and outcomes are still in evolution. STUDY: Medical records and images were reviewed for all patients diagnosed with ERF at Mayo Clinic in Rochester, MN, between September 1, 2001 and January 1, 2012. Fistulas were classified as malignant or benign. Treatment strategies were classified as surgical or nonsurgical (typically esophageal stent placement). Technical and clinical success, survival, and survival free of second intervention were assessed. RESULTS: A total of 123 patients with acquired ERF were identified, of whom 65 (53%) were malignant and 58 (47%) benign. Initial treatment strategy was nonsurgical in 88 (72%) patients and surgical in 35 (28%); lower Charlson comorbidity scores were associated with increased likelihood of surgery. Technical and clinical success was seen in a majority of patients treated both surgically and nonsurgically. Patients with malignant ERF treated surgically survived longer than patients undergoing nonsurgical treatment (hazard ratio=5.6, P=0.005). In contrast, those with benign ERF had similar overall survival regardless of whether they received initial surgical or nonsurgical treatment; reintervention was more common in those who underwent nonsurgical treatment (hazard ratio=2.3, P=0.03). CONCLUSIONS: We conclude that survival in malignant ERF is better with surgical intervention in selected patients. Surgical and nonsurgical techniques achieve similar survival in benign ERF, but reintervention is more common in those treated endoscopically.

A 39-Year-Old Pregnant Woman with Pulmonary Emboli on Long Term Anticoagulation.

We present the case of a 39-year-old pregnant woman with Klippel-Trenaunay syndrome (KTS). We demonstrate the risks of multiple, co-existing pro-thrombotic states (pregnancy, KTS), discuss complications of KTS (deep venous thromboembolisms and pulmonary emboli) and highlight general and disease-specific preventive measures against venous thromboembolic events (VTE). KTS is a rare condition and it's co-existence with pregnancy and VTEs is rarer still.

Outpatient thoracoscopy: safety and practical considerations.

PURPOSE OF REVIEW: Medical thoracoscopy, also known as pleuroscopy, has been utilized by chest physicians for more than a century. Despite this, it has only recently re-emerged as an important tool for interventional pulmonologists to diagnose and treat pleural diseases. The purpose of this review is to critically assess the recent literature related to medical thoracoscopy, specifically as it pertains to its safety and feasibility as an outpatient procedure. RECENT FINDINGS: Recent data have reaffirmed the clinical utility of medical thoracoscopy and suggest that it can be safely performed in an outpatient setting. A single-center study of 51 patients published in the past year described both the feasibility and safety of outpatient medical thoracoscopy. This study highlights the notion that the majority of patients do not require hospital admission after a routine diagnostic thoracoscopy in the absence of talc poudrage. Another study this year described the successful use of chest physician-directed ultrasound-guided cutting needle biopsy when medical thoracoscopy was not technically possible. SUMMARY: The contribution of medical thoracoscopy in the diagnosis and management of pleural diseases is increasingly recognized. Evidence supports the routine practice of medical thoracoscopy on an outpatient basis in experienced centers.

Impact of pleural manometry on the development of chest discomfort during thoracentesis: a symptom-based study.

BACKGROUND: Routine manometry is recommended to prevent complications during therapeutic thoracentesis, but has not definitively been shown to prevent pneumothorax or reexpansion pulmonary edema. As chest discomfort correlates with negative pleural pressures, we aimed to determine whether the use of manometry could anticipate the development of chest discomfort during therapeutic thoracentesis. METHODS: A retrospective chart review of 214 consecutive adults who underwent outpatient therapeutic thoracentesis at our institution between January 1, 2011 and June 30, 2013 was performed. We compared preprocedural to postprocedural discomfort (using a linear analog scale from 0 to 10) in patients undergoing thoracentesis with or without manometry. We used a multivariate model to adjust for possible confounders. Changes of dyspnea scores were also analyzed. RESULTS: Manometry was performed in 82/214 patients (38%). On univariate and multivariate analyses, neither the change in chest discomfort nor dyspnea scores was significantly different in the manometry versus the control group (P=0.12 and 0.24, respectively). Similar results were also found in the subgroup of large-volume thoracentesis (P=0.32 for discomfort, P=1.0 for dyspnea). CONCLUSIONS: In our retrospective study, the use of manometry did not appear to anticipate the development of chest discomfort during therapeutic thoracentesis. Prospective studies are needed to confirm these findings.

The role of interventional therapy for pleural diseases.

Pleural diseases encompass a vast and heterogeneous group of diseases that have traditionally received relatively little attention from researchers, resulting in empiric approaches to patient management based largely on expert opinions and anecdotal evidence. Yet, paradoxically, pleural diseases represent a considerable burden for patients, providers, and the healthcare system as a whole, with a rising incidence of malignant pleural effusions and pleural space infections, in increasingly complex patients. Fortunately, the last decade has witnessed unprecedented research efforts from the pleural community, which have resulted in substantial advances in risk-stratification, patient selection, treatment efficacy and the development of evidence-based recommendations ultimately leading to improved patient care. In this review, we will present a summary of the current evidence for the management of pleural diseases with an emphasis on interventional procedures, and highlight the need for future research efforts in the field of malignant pleural effusions, pleural space infections and pneumothorax.

Nonspecific pleuritis: optimal duration of follow-up.

BACKGROUND: Nonspecific pleuritis (NSP) is a frequent diagnosis after parietal pleural biopsy, but the clinical significance of this finding and need for further follow-up have not been firmly established. Previous reports suggest that 5% to 25% of patients with NSP are subsequently diagnosed with pleural malignancy. METHODS: Our pathology database was queried for patients with histologic evidence of NSP from January 01, 2001, to December 31, 2012 (n = 413). Patients with less than 1 year of follow-up after biopsy, diagnosis of empyema, tuberculous pleuritis, active systemic connective tissue disease or vasculitis, or active malignancy were excluded (n = 327). The remaining patients were included and their medical records were reviewed. RESULTS: Eighty-six patients were included. Mean follow up was 1,824 ± 1,032 days (range, 409 to 4,599 days). Three of the 86 patients with NSP (3.5%) were subsequently diagnosed with pleural malignancy. All 3 patients were found to have mesothelioma with a mean time from biopsies to diagnosis of 205 ± 126 days (range, 64 to 306 days). Twenty-two of 86 patients (25.5%) had a possible identifiable cause of pleural inflammation (benign disease). After exclusion of these 22 patients, the incidence of malignancy was 3 of 64 (4.7%). CONCLUSIONS: The incidence of subsequent pleural malignancy (mesothelioma) among patients found to have NSP based on pleural biopsy was 3.5%. Occult mesothelioma in patients with NSP will most likely be diagnosed within 1 year of the initial pleural biopsy; therefore, these patients should be followed for a minimum of 1 year to allow for timely detection of occult pleural malignancy.

Feasibility and safety of outpatient medical thoracoscopy at a large tertiary medical center: a collaborative medical-surgical initiative.

BACKGROUND: Medical thoracoscopy (MT) is performed by relatively few pulmonologists in the United States. Recognizing that an outpatient minimally invasive procedure such as MT could provide a suitable alternative to hospitalization and surgery in patients with undiagnosed exudative pleural effusions, we initiated the Mayo Clinic outpatient MT program and herein report preliminary data on safety, feasibility, and outcomes. METHODS: All consecutive patients referred for outpatient MT from October 2011 to August 2013 were included in this study. Demographic, radiographic, procedural, and histologic data were recorded prospectively and subsequently analyzed. RESULTS: Outpatient MT was performed on 51 patients, with the most common indication being an undiagnosed lymphocytic exudative effusion in 86.3% of the cohort. Endoscopic findings included diffuse parietal pleural inflammation in 26 patients (51%), parietal pleural studding in 19 patients (37.3%), a normal examination in three patients (5.9%), diffuse parietal pleural thickening in two patients (3.9%), and a diaphragmatic defect in one patient (2%). Pleural malignancy was the most common histologic diagnosis in 24 patients (47.1%) and composed predominantly of mesothelioma in 14 (27.5%). Nonspecific pleuritis was the second most frequent diagnosis in 23 patients (45.1%). There were very few complications, with no significant cases of hemodynamic or respiratory compromise and no deaths. CONCLUSIONS: Outpatient MT can be integrated successfully into a busy tertiary referral medical center through the combined efforts of interventional pulmonologists and thoracic surgeons. Outpatient MT may provide patients with a more convenient alternative to an inpatient surgical approach in the diagnosis of undiagnosed exudative pleural effusions while maintaining a high diagnostic yield and excellent safety.

Determinants of gait speed in COPD.

BACKGROUND: Measures of physical function, daily physical activity, and exercise capacity have been proposed for the care of patients with COPD but are not used routinely in daily office care. Gait speed is a powerful and simple measure of physical function in elderly patients and seems to be a promising measure for the daily care of patients with COPD. The objective of this study was to comprehensively evaluate the determinants and factors influencing gait speed in COPD, particularly the association of gait speed with objectively measured physical activity and the most used exercise capacity field test in cardiopulmonary disease: the 6-min walk test (6MWT). METHODS: One hundred thirty patients with stable COPD performed two different 4-m gait speed protocols (usual and maximal pace). We modeled gait speed using demographics, lung function, dyspnea, quality of life, physical activity monitoring, exercise capacity, mood, cognitive function, and health-care use. RESULTS: Gait speed was independently associated with 6MWT but not with daily physical activity. The correlation between gait speed and 6MWT was high regardless of protocol used (r = 0.77-0.80). Both 6MWT and gait speed shared similar constructs. Gait speed had an excellent ability to predict poor (≤ 350 m) or very poor (≤ 200 m) 6MWT distances (areas under the curve, 0.87 and 0.98, respectively). Gait speed was not independently associated with quality of life, mood, or cognitive function. CONCLUSIONS: Gait speed is more indicative of exercise capacity (6MWT) than daily physical activity in COPD. Despite its simplicity, gait speed has outstanding screening properties for detecting poor and very poor 6MWT performance, making it a useful and informative tool for the clinical care of patients with COPD.

Measuring gait speed in the out-patient clinic: methodology and feasibility.

BACKGROUND: Gait speed is a simple physical function measure associated with key outcomes in the elderly population. Gait speed measurements may improve clinical care in patients with COPD. However, there is a knowledge gap about the reliability and variability of gait speed testing protocols in COPD. We evaluated established techniques of measuring gait speed in patients with COPD and assessed feasibility of implementing gait speed as a routine vital sign in an out-patient clinic. METHODS: The usual 4-meter gait speed (4MGS) ("walk at a comfortable/natural pace"), maximal 4MGS ("walk as fast as you can safely"), usual 10-meter gait speed (10MGS), and maximal 10MGS of subjects with stable COPD were measured. Walks were measured using a stopwatch and automated timing system. For the feasibility/implementation phase, patients from the entire spectrum of respiratory diseases completed acceptability surveys, and clinical assistants administered gait speed measurements using an automated timing system. Time to train and to administer the test and acceptability by the staff were evaluated. RESULTS: Seventy subjects enrolled; 60% were men, and the mean age ± SD was 69 ± 10 years. All methods showed excellent test-retest reliability (intraclass correlation coefficient of 0.95-0.97). The difference between the two timing systems did not exceed the suggested minimal clinically important difference of 0.1 m/s for the usual pace instructions but did exceed 0.1 m/s for maximal pace walks. The difference between 4MGS and 10MGS was 0.13 ± 0.10 m/s. FEASIBILITY: Most subjects reported that gait speed measurement prior to clinic appointment was very acceptable (66%) or acceptable (33%). Time added to clinic visit measuring 4MGS was 95 ± 20 seconds, and clinical assistants reported gait speed measurements as very acceptable (60%), acceptable (30%), and somewhat acceptable (10%). CONCLUSIONS: Gait speed is a reliable measure in COPD, regardless of instructed pace, distance, or timing mechanism; however, adhering to one protocol is suggested. 4MGS was easily implemented into clinical practice with high acceptability by patients and clinic staff.

Idiopathic subglottic stenosis: an evolving therapeutic algorithm.

OBJECTIVES/HYPOTHESIS: Idiopathic subglottic stenosis (ISS) is a rare type of airway stenosis of unclear etiology. Open resection, while effective, remains a complex surgery and requires a hospital stay. Endoscopic management is often preferred but has historically been associated with a high recurrence rate. We aimed to analyze our experience, consisting of a standardized endoscopic approach combined with an empiric medical treatment. STUDY DESIGN: Retrospective cohort study. METHODS: All patients with ISS managed with standardized endoscopic treatment at our institution between 1987 and 2012 were identified, and their electronic medical records were reviewed. The treatment consisted of CO2 laser resection without dilatation and local infiltration with steroids and application of mitomycin C. Patients were also treated with antireflux medications, inhaled corticosteroids, and occasionally trimethoprim-sulfamethoxazole. The influence of medical management on annual recurrence rate was analyzed using negative binomial logistic regression. RESULTS: A total of 110 patients treated with standardized endoscopic management were included in our analysis. The procedure was well tolerated by all patients without complications. Recurrences were observed in approximately 60% of patients at 5 years. There was a trend suggesting an association between aggressive medical treatment and a reduction in the rate of recurrence/person/year (relative risk = 0.52, P = 0.051). CONCLUSION: A standardized endoscopic management of ISS consisting of CO2 laser vaporization of the fibrotic scar appears effective in symptom control, with 40% of patients not requiring retreatment in the follow-up period, and with recurrence noted in a majority of patients. Aggressive medical treatment may have a role, but further prospective studies are required to confirm these findings. LEVEL OF EVIDENCE: 4.

Correlations between gait speed, 6-minute walk distance, physical activity, and self-efficacy in patients with severe chronic lung disease.

BACKGROUND: Four-meter gait speed (4MGS) has been associated with functional capacity and overall mortality in elderly patients, and may easily be translated to daily practice. We evaluated the association of 4MGS with meaningful outcomes. METHODS: In 70 subjects we conducted the 4MGS, 6-min walk test (6MWT), objectively measured physical activity, and assessed dyspnea, quality of life, and self-efficacy for walking and routine physical activity. 4MGS was measured in 3 separate time epochs during the 6MWT, to explore 4MGS variability. RESULTS: Diagnoses included COPD (51.4%), interstitial lung disease (38.6%), and other pulmonary conditions (10%). The mean ± SD values were: 4MGS 0.85 ± 0.21 m/s, 6-min walk distance (6MWD) 305 ± 115 m, and physical activity level 1.28 ± 0.17, which is consistent with severe physical inactivity. The gait speeds within the time epochs 1-2, 3-4, and 5-6 min during the 6MWT were not significantly different: 1.01 ± 0.29 m/s, 0.98 ± 0.31 m/s, and 1.00 ± 0.31 m/s, respectively. 4MGS had a significant correlation with 6MWD (r = 0.70, P < .001). 6MWD was the dominant variable for predicting 4MGS. Other significant predictors of 4MGS included dyspnea, self-efficacy, quality of life, and objectively measured physical activity. CONCLUSIONS: 4MGS is significantly and independently associated with 6MWD, and may serve as a reasonable simple surrogate for 6MWD in subjects with chronic lung disease. Gait speed was remarkably stable throughout the 6MWT, which supports the validity of an abbreviated walk test such as 4MGS.

The role for tunneled indwelling pleural catheters in patients with persistent benign chylothorax.

BACKGROUND: Utilization of tunneled indwelling pleural catheters (TIPCs) for persistent pleural effusions is increasingly more common; however, the presence of chylothorax is generally considered a contraindication for utilization of a TIPC due to concerns regarding potential nutritional, immunologic and hemodynamic complications. Therefore, in this study, a cohort of patients with persistent benign chylothorax managed with TIPCs is described. METHODS: A retrospective analysis of patients with persistent benign chylothorax managed with a TIPC at the study center between January 1, 2008, and March 1, 2012, was completed. Extracted data included patient characteristics, chylothorax etiologies, prior interventions, outcomes and complications. RESULTS: Eleven patients (14 hemithoraces) had persistent benign chylothorax treated with placement of a TIPC during the inclusion time frame. Etiology of the chylothorax was nontraumatic in 8 of the 11 patients, with the remaining 3 secondary to thoracic surgery. Pleurodesis was achieved in 9 of the 14 hemithoraces, with a median time to pleurodesis of 176 days. All procedures were well tolerated, and no immediate periprocedural complications were reported. One serious complication was encountered in the form of a postoperative pulmonary embolism after replacement of an occluded TIPC, resulting in the patient's death. Two patients had transient occlusions of their TIPCs successfully treated with intracatheter thrombolytic therapy. No significant adverse nutritional, hemodynamic or immunologic outcomes were reported during follow-up for any included patient. CONCLUSIONS: Utilization of a TIPC for the management of persistent benign chylothorax should be considered early because pleurodesis may be frequently and safely achieved in this patient population.

Screening for severe physical inactivity in chronic obstructive pulmonary disease: the value of simple measures and the validation of two physical activity questionnaires.

Objectively measured severe physical inactivity (SPI) has been reported as the strongest independent predictor of mortality in patients with chronic obstructive pulmonary disease (COPD). Activity monitoring is not feasible in routine clinical practice; therefore, we set out to determine the utility of simple clinical measures for predicting SPI in patients with COPD. A total of 165 patients with COPD wore an activity monitor for 5 days to define the presence or absence of SPI. Logistic models were generated including the modified Medical Research Council (MMRC) dyspnea grade, spirometry and the age-dyspnea-airflow obstruction (ADO) index. Physical Activity Scale for the Elderly (PASE) and Stanford Brief Activity Scale (SBAS) were also tested for validity and reliability in a subgroup of 67 patients. The MMRC dyspnea grade, PASE score, ADO index and SBAS score were associated with SPI, but general self-efficacy and spirometry were not. An MMRC dyspnea grade ≥3 was the best independent predictor of SPI (AUC: 0.74; PPV: 0.83; NPV: 0.68) followed closely by a PASE score of <111. The combination of MMRC dyspnea grade and PASE score provided the most robust model (AUC: 0.83; Positive Predictive Value (PPV): 0.95; Negative Predictive Value (NPV): 0.63). The results were confirmed using 5000 bootstrapped models from the cohort of 165 patients. MMRC dyspnea grade ≥3 may be the best triage tool for SPI in patients with COPD. The combination of the MMRC and PASE score provided the most robust prediction. Our results may have significant practical applicability for clinicians caring for patients with COPD.