CHEST 2020
The CHEST Annual Meeting 2020 virtual event, held October 18-21, 2020, featured numerous educational sessions and lectures in pulmonary, critical care, and sleep medicine. Here are highlights from select presentations.
- Aggressive management of ILD as a complication of idiopathic inflammatory myopathies can maintain lung function
- Current lung cancer screening guidelines may miss significant number of African Americans at risk
- Switch to riociguat may benefit PAH patients not at treatment goal on PDE5 inhibitor
- Viral pneumonia severity score predicts outcomes in COVID-19 pneumonia
- VTE risk score and bleeding risk score may inform thromboprophylaxis decision post-discharge
- Benefit of phrenic nerve stimulation on central sleep apnea sustained to 5 years
Aggressive management of ILD as a complication of idiopathic inflammatory myopathies can maintain lung function
Presenter: Hema Balina, MD
A single-center retrospective study suggests that aggressive management of idiopathic inflammatory myositis (IIM)-related interstitial lung disease (ILD) may preserve lung function and reduce the rate of death.1
ILD is a complication in patients with IIM, and the mortality rate of IIM-related ILD is about 80%, said Hema Balina, MD, from the University of Alabama at Birmingham (UAB), who presented the findings from the UAB experience.
A total of 32 patients with IIM-related ILD between 2014 and 201 formed the study cohort. Their charts were examined for demographic data and treatment data, and the results from spirometry and the 6-minute walk test as well as response to treatment were evaluated at each patient visit. Patients were followed for at least 3 years after diagnosis until March 2020 or death.
Mean age of the cohort at time of diagnosis was 51.1, the ratio of men to women was 30 to 70, 61% were African American, mean body mass index was 29.8 kg/m2, mean forced vital capacity (FVC) was 56%, and mean diffusing capacity for carbon monoxide was 45%.
“All of these patients had serologic evidence of myositis-specific antibodies or myositis-associated antibodies and elevated [creatine kinase] levels; however, the ILD diagnosis was made prior to the development of myositis in 48% of patients,” said Dr. Balina. This percentage is far higher than the 20% reported in the literature, she noted.
Prednisone was used as part of a tapered treatment regimen with steroid-sparing agents in 84% of the patients. Azathioprine was chosen as first-line treatment in 55% of patients and mycophenolate mofetil in 36%. In the remaining 9% of patients, either cyclophosphamide or methotrexate was chosen.
The treatment regimen was changed in 67% of patients, and the changes were mainly secondary to lack of response or deterioration of lung function (n = 10) or intolerance to side effects (n = 9). “In only a few patients was treatment changed due to socioeconomic factors,” said Dr. Balina.
Rituximab was used in ILD refractory to first-line immunosuppression in 34% (n = 11) of patients and in 2 others who could not tolerate other agents.
An improvement in pulmonary function was noted with aggressive treatment, she said. The mean change in FVC at the end of follow-up (83 months) was 0.61 ±0.5 L/min. Disease worsening was observed in 37% of patients. Only 3 patients had died at the end of the follow-up period.
In addition to aggressive management, the study shows that frequent monitoring of treatment response can improve outcomes in IIM-related ILD, Dr. Balina concluded.
Reference
1. Balina H, Dsouza K, Acosta Lara P, Luckhardt T, Kulkarni T, Gulati S. Natural history of interstitial lung disease (ILD) and response to treatment regimens in patients with idiopathic inflammatory myopathies (IIM): a single center experience. CHEST 2020; 158(4 Suppl):A1046–A1047. doi:https://doi.org/10.1016/j.chest.2020.08.971
Current lung cancer screening guidelines may miss significant number of African Americans at risk
- High-risk group 1 consists of individuals ages 55 to 74 with a 30 pack-year smoking history and either a current smoker or one who quit smoking within the past 15 years. High-risk group 2 comprises individuals age 50 and older with a smoking history of at least 20 pack-years and additional risk factors that increase the risk of lung cancer to 1.3% or greater. According to NCCN, high-risk group 1 and 2 are eligible for annual low-dose CT.
- Lung cancer screening is not recommended for those age 50 and older with a smoking history of at least 20 pack-years and no additional risk factors, labeled the moderate-risk group, or a low-risk group consisting of individuals age 50 or younger with or without a smoking history of less than 20 pack-years.
Reference
1. Velez Martinez C, Thurlapati A, Hirani S, et al. Do our current USPSTF guidelines for lung cancer screening fail young, high-risk African American smokers? CHEST 2020; 158(4 Suppl):A1454–A1455. doi:https://doi.org/10.1016/j.chest.2020.08.1313
Switch to riociguat may benefit PAH patients not at treatment goal on PDE5 inhibitor
Reference
1. Hoeper M, Ghofrani H, Al-Hiti H, et al. Switching to riociguat in patients with pulmonary arterial hypertension not at treatment goal with phosphodiesterase type-5 inhibitors: subgroup analysis results of the REPLACE study. CHEST 2020; 158(4 Suppl):A2156–A2159. doi:https://doi.org/10.1016/j.chest.2020.08.1857
Viral pneumonia severity score predicts outcomes in COVID-19 pneumonia
Presenter: Jurgena Tusha, MD
The recently developed MuLBSTA score, which incorporates six clinical parameters, predicts disease severity and overall outcomes in patients with COVID-19 pneumonia.
In a retrospective study conducted at a community hospital in Michigan,1 a significant positive correlation was found between the MuLBSTA score and death in hospitalized patients with COVID-19 pneumonia, according to data presented by Jurgena Tusha, MD, from Wayne State University, Detroit.
An influx of SARS-CoV-2 infection has led to several unanswered questions. “One question raised was how to risk-stratify these patients in order to direct further management,” she said. “The score correlated significantly with mortality, ventilator support, and length of stay, which may be used to provide guidance to screen patients and make further clinical decisions.”
The MuLBSTA score was developed in China and is designed to predict 90-day mortality in patients with viral pneumonia. It is based on six factors: multilobe infiltrate, which is weighted the most (5 points); absolute lymphocyte count ≤ 0.8 x 109/L (4 points); bacterial coinfection as detected by sputum or blood culture (4 points); smoking history (2 points for prior smoker, 3 points for active smoker); history of hypertension (2 points); and age ≥ 60 (2 points). The maximum score is 20.
For the study, 163 charts from hospitalized patients with COVID-19 pneumonia from March 15 to April 10, 2020 were reviewed manually. Length of stay outside the intensive care unit (ICU) was 6.46 days and ICU length of stay was 15.5 days. Median age of the 55 patients in the ICU was 68 years. Mechanical ventilation was employed in 78.2% of ICU patients. The overall mortality rate of the cohort was 29.4%, the ICU mortality rate was 50.9%, and the ventilator-associated mortality was 62.8%.
The MuLBSTA score was applied to each patient at the time of hospitalization. The mean MuLBSTA score was 8.67 for patients who survived and 13.6 for those who died. The correlation between MuLBSTA score and mortality was significant (odds ratio [OR] 1.37; 95% confidence interval [CI] 1.23–1.53; P = .0001). The area under the receiver operating characteristic curve of MuLBSTA for predicting in-hospital death at the time of admission was 0.813 (95% CI, 0.74-0.885). The investigators also found a positive correlation between the MuLBSTA score and ventilator support (OR 1.30; 95% CI 1.17–1.44; P = .0001) and length of stay (r [161] = .35; P = .0001). Kaplan-Meier survival analysis showed that patients with a MuLBSTA score greater than 12 had a higher risk of death compared with those with a score 12 or lower (P = .001).
“I thought this was very interesting because this score takes into account some of the factors that make COVID-19 a unique disease, and age and hypertension were included in the score,” said Marc Feinstein, MD, a critical care medicine specialist at Memorial Sloan Kettering Cancer Center in New York City, who moderated the session. Modifying the score based on risk factors unique to COVID-19, such as obesity, other forms of lung disease, and history of coronary heart disease, may improve the ability of the score to predict COVID-19 outcomes, he and Dr. Tusha agreed.
“So far, we haven’t developed any other scores or expanded on this specific score, but we’re trying to see if it does apply to perhaps stratify which patients get which types of treatment,” said Dr. Tusha. “That would be something for the future.”
Reference
1. Hoeper M, Ghofrani H, Al-Hiti H, et al. Switching to riociguat in patients with pulmonary arterial hypertension not at treatment goal with phosphodiesterase type-5 inhibitors: subgroup analysis results of the REPLACE study. CHEST 2020; 158(4 Suppl):A2156–A2159. doi: https://doi.org/10.1016/j.chest.2020.08.1857
VTE risk score and bleeding risk score may inform thromboprophylaxis decision post-discharge
Presenter: Scott Woller, MD
In hospitalized medical patients, the risks of 90-day hospital-associated venous thromboembolism (HA-VTE) and hospital-associated major bleeding (HA-MB) can be estimated at the time of discharge through the use of a risk-estimation tool, based on ubiquitous laboratory values, to inform decisions on extended duration thromboprophylaxis, according to a model presented by Scott Woller, MD, from Intermountain Health Care, Murray, UT.
Further, with broad adoption of electronic medical records, risk of these outcomes could be assessed with no additional time or expense, he said.
From 50% to 75% of all HA-VTE events occur after hospital discharge. “Yet evidence suggests that there is a narrow margin that exists between the outcomes of bleeding and thrombosis when post-discharge thromboprophylaxis is administered,” said Dr. Woller. “So the real conundrum is, How do we identify those patients that would best benefit from extended- duration thromboprophylaxis (EDT) without bleeding complications?”
Current VTE risk scores, such as the Modified IMPROVE VTE risk score that incorporates D-dimer, have enduring limitations that include the difficulty of using computerized interrogation to identify VTE clinical risk factors and inclusion of a measurement (D-dimer) that is not routinely obtained in clinical practice.
“What we were especially interested in doing is understanding if we could generate a risk score from common covariates that are ubiquitously available in routine clinical care,” he said. “We found that those that were most predictive of VTE and major bleeding 90 days post-discharge were age, white blood cell count, red cell distribution width, platelet count, blood glucose, sodium, and creatinine.”
The Intermountain risk score (IMRS) is a highly predictive mortality risk estimation tool derived from components of the complete blood cell count and the basic metabolic panel. The research team generated VTE and bleeding risk scores as refinements to the IMRS, reweighing components from the complete blood cell count and basic metabolic panel to be predictive of 90-day outcomes.1
Their dataset included 45,669 medical patients who survived hospitalization in which 1,038 (1.6%) VTE and 611 (1.3%) major bleeding events were recorded. This cohort was split into derivation and validation cohorts. A Cox model was fit in the entire derivation cohort with covariates that included red cell distribution width, blood urea nitrogen, age, glucose, white blood cell count, platelet count, red blood cell count, sodium, and creatinine. The complete blood cell count and basic metabolic panel candidate variables were split into quintiles. Each quintile was weighted based on “predictiveness,” and points were assigned from 0 for the least predictive quintile (referent) to a maximum of 5.
A 90-day VTE rate of 2% was selected as clinically important, and correlated to an IMRS of 7. A 90-day major bleeding rate of 1% was selected as clinically important, and correlated to an IMRS of 8.
In the derivation set, an HA-VTE IMRS of 7 or higher was associated with an area-under-the-receiver-operating-characteristic curve (AUC) of 0.646, and an HA-MB IMRS of at least 8 was associated with an AUC of 0.692. In the validation cohort, an HA-VTE IMRS of 7 or higher generated an AUC of 0.60, and an HA-MB IMRS of 8 or higher generated an AUC of 0.643.
Survival at 90 days free from VTE was 1.6% in patients with an HA-VTE IMRS less than 7 and 2.6% in those with an HA-VTE IMRS of 7 or higher (hazard ratio 1.69; 95% confidence interval 1.35–2.13). Major bleeding in patients HA-MB IMRS of 8 or higher occurred at a rate of 1.9% vs 0.8% in those with an HA-MB IMRS less than 8 (hazard ratio 2.35; 95% confidence interval 1.75–3.16).
“If validated, the strength of this work will be that we will be able to present to physicians, in a ‘just-in-time’ fashion, individual patient risk for thrombosis within 90 days after discharge, but also the risk for major bleeding,” said Dr. Woller. “Because of the narrow margin that exists between thrombosis risk and bleeding risk in discharged hospitalized medical patients, this could help inform optimal care.”
REFERENCE
1. Woller D, Stevens S, Snow G, et al. Derivation and validation of the HA-VTE and HA-MB Intermountain risk scores from ubiquitous clinical biomarkers to predict 90-day hospital-associated venous thromboembolism and major bleeding among medical patients. CHEST 2020; 158(4 Suppl]:A2452–A2453. DOI:https://doi.org/10.1016/j.chest.2020.09.034
Benefit of phrenic nerve stimulation on central sleep apnea sustained to 5 years
Presenter: Shahrokh Javaheri, MD
At 5 years, patients with moderate to severe central sleep apnea who underwent transvenous phrenic nerve stimulation showed durability of improvements in the apnea-hypopnea index (AHI), sleep arousals, daytime sleepiness, and other outcomes.1 Further, 78% of patients were still alive at the 5-year follow-up, including 68% of those with heart failure, reported Shahrokh Javaheri, MD, from the Division of Pulmonary and Sleep Medicine, Bethesda North Hospital, Cincinnati, OH.
The implantable transvenous phrenic nerve stimulation device (remedē System; Respicardia Inc.) was approved by the US Food and Drug Administration (FDA) in 2017 for the treatment of severe central sleep apnea in adults. The device, implanted similar to the way a pacemaker is implanted, stimulates the phrenic nerve to activate the diaphragm, thereby restoring a more normal breathing pattern during sleep.
As a condition of FDA approval, data from the 6-month randomized controlled trial on which approval was based were collected through 5 years postimplant to assess long-term safety, effectiveness, and mortality. All patients in the follow-up were randomized to active therapy in the controlled trial.
At 5 years, the median number of AHI events per hour in a paired sample of 42 patients with 5-year polysomnograms decreased from 42/hour at baseline to 17/hour at 5 years (median change [interquartile range], -22/hour; P < .001). The reduction occurred predominantly in central apnea events, with little change in the obstructive apnea index, said Dr. Javaheri.
Parallel changes in the arousal index were observed. In a paired analysis of 35 patients, the arousal index decreased from a median of 36/hour at baseline to 23/hour at 5 years, for a median reduction [interquartile range] of 14/hour (P < .001).
“Consistent with the reduction in AHI over 5 years was a progressive improvement in sleep architecture,” he said, with a shift away from light-stage sleep (N1) to deeper-stage sleep (N2-REM). Paired analysis of 35 patients showed a median reduction in N1 sleep of 19% at 5 years and a median increase in REM sleep of 14%.
At baseline, 45% of the 131 patients enrolled had an Epworth Sleepiness Scale (ESS) score greater than 10. At 5 years, 62% of patients with a baseline score greater than 10 shifted to a score of 10 or lower. Paired changes in ESS from baseline in 50 patients showed a median reduction in ESS score from 12 at baseline to 6 at year 5 (median change [interquartile range] -3; P < .001).
An independent clinical events committee found no unanticipated adverse device effects and no deaths related to the implant procedure, device, or delivered therapy. Most serious adverse events occurred in the first year after implantation. With increased experience in implanting the device, the number of side effects has been reduced, said Dr. Javaheri. Beyond 3 years, there were 2 stimulation lead component failures and 1 lead dislocation that required surgical replacement, and 1 implant site infection.
In randomized controlled trials, use of continuous positive airway pressure in patients with sleep apnea has been associated with excess mortality, noted Dr. Jahaveri. “One of the hypotheses was that with positive airway pressure therapy, the increased intrathoracic pressure could result in adverse effects, particularly in the subset of patients with heart failure,” he said. “Therefore, therapeutic modalities that do not cause increased intrathoracic pressure, such as oxygen therapy, medications, or phrenic nerve stimulation, could have a different impact.”