James Davidson, M.D. – Message from the President
Hello and welcome from the North Carolina Thoracic Society (NCTS). As your state chapter of the American Thoracic Society, we strive to bring you high value content within the topics of Pulmonary, Critical Care and Sleep medicine while simultaneously building a community of providers that span the state and integrate our outstanding academic medical centers with our exceptional private practice groups both large and small. This focus on community building through outreach efforts have become even more important during this past year with the struggles we’ve all faced battling COVID-19.
The NCTS’ past year has been highlighted by some fantastic educational events including our ‘Meet the Professor’ talk on severe asthma talk in Asheville and our NCTS 2020 Annual Educational Conference held virtually from the campus of Duke University. We enjoyed fantastic talks on, among other topics, lung cancer screening, antifibrotics in ILD, age-related factors in lung disease, and a COVID-19 countermeasure and vaccine update. Moving forward, our aim will be to continue our efforts of community building, educational outreach, and knowledge sharing as we embark on one of the most uncertain years we as providers have faced. To continue this success, we hope that you will seriously consider joining the NCTS for only $50 annually. Go to www.NCTHORACIC.org to review our up to date content and find a membership application.
Regardless of membership status, we would love to see you at this year’s annual education conference in October 2021 which will be held in beautiful Asheville, NC which was recently named one of the top 10 best mountain towns in the US by Thrillist. https://www.thrillist.com/travel/nation/the-best-mountain-towns-in-america
Sincerely,
James Davidson
Chapter President 2020-2021 Fall 2020 NCTS Newsletter
NCTS Events and Announcements
New Secretary/Treasurer: Praveen Mannam, MD
We would like to welcome Praveen as the newest officer of NCTS. Praveen has been a pulmonologist at Cone Health since 2016 with interests in critical care, severe asthma and interstitial lung diseases. Praveen completed his medicine residency at Drexel University and fellowship in Pulmonary and Critical Care at Yale University in 2010. After fellowship he joined the faculty at Yale School of Medicine where among other activities, he was involved in molecular research in innate immune mechanisms of acute lung injury. Praveen is the assistant director of the Pulmonary Fibrosis Center at Cone Health.
Membership in NCTS
If you are already an NCTS member, we thank you for your support and hope that you will share this newsletter with a colleague! If you are considering becoming a member for only $50/year – which also covers the cost of attending the annual meeting and the associated Category I CME – then please do one of the following:
1. check out our website www.NCTHORACIC.org
2. simply go to this direct link: https://www.thoracic.org/members/chapters/thoracicsociety-chapters/north-carolina, or
3. visit our facebook page https://www.facebook.com/NCthoracicsociety/
North Carolina Thoracic Society’s 2020 Virtual Annual Educational Conference – Duke University Durham, NC
The NCTS held its annual educational virtually from the Hanes House at Duke University. As pointed out by our President we had some outstanding talks that were very relevant to both practitioners and researchers involved in lung health. It was the first year that we had a patient share their perspective. Fred shared his experience with pulmonary fibrosis support groups in NC.
As we went from a live program to virtual, it was a challenge to speakers, program coordinators and sponsors, adjusting to the new format of such programs. Our confidence in holding a virtual conference was greatly enhanced to the point that we expect even live programs will have a virtual component. Hopefully this will make our program more accessible across the state. Fall 2020 NCTS Newsletter
2021 North Carolina Thoracic Society Annual Educational Conference
Next year’s annual conference is being planned for Asheville, North Carolina Fall 2021. We anticipate it will be a combined live and virtual meeting or virtual meeting.
ADVANCES IN THERAPIES
The Future of Augmentation Therapy in Alpha-1 Antitrypsin Deficiency
M. Bradley Drummond, MD MHS University of North Carolina at Chapel Hill Brad_Drummond@med.unc.edu
Severe α1-antitrypsin deficiency (AATD), estimated to be present in 100,000 US individuals, increases risk of chronic lung disease include emphysema, bronchiectasis and airflow obstruction. Criteria to screen for AATD are outlined by several societies 1-3 and include: all individuals with chronic obstructive pulmonary disease (COPD) or emphysema, especially at younger age or without risk factors; unexplained bronchiectasis; granulomatosis with polyangiitis; or unexplained cirrhosis. Augmentation therapy is generally recommended for individuals with severe AATD (serum AAT <57 mg/dL) and FEV1 in the range of 30-65% predicted, with consideration of augmentation therapy in other patient groups.2 The four current FDA-approved augmentation products are derived from pooled human α1-antitrypsin, administered at 60 mg/kg weekly via intravenous infusion.
Many challenges exist with the currently available infusion therapies. Lifelong weekly infusions are burdensome for patients and increase healthcare costs. Some patients require port implantation for recurrent venous access necessary for treatment. Oral therapies to treat AATD have the potential to substantially decrease these challenges. Potential new approaches to treat AATD include aerosolized AAT, gene therapy to augment normal AAT synthesis, and oral treatments. There are several actively recruiting trials of oral therapies for AATD in North Carolina.4-6 The drugs studied in these clinical trials approach treatment of AATD with small Fall 2020 NCTS Newsletter
molecules targeting the AAT protein folding defect7 or with an oral neutrophil elastase inhibitor.8 Given the lifelong burden of treatment for AATD and the need for novel therapies for
this disease, the NC Thoracic Society encourages you to inform your AATD patients of these ongoing trials and facilitating engagement with recruiting sites through online resources (www.alpha1trial.com or participating center listed on www.clinicaltrials.gov).
References
1. Miravitlles M, Dirksen A, Ferrarotti I, et al. European Respiratory Society statement: diagnosis and treatment of pulmonary disease in alpha1-antitrypsin deficiency. Eur Respir J. 2017;50(5).
2. Sandhaus RA, Turino G, Brantly ML, et al. The Diagnosis and Management of Alpha-1 Antitrypsin Deficiency in the Adult. Chronic Obstr Pulm Dis. 2016;3(3):668-682.
3. American Thoracic S, European Respiratory S. American Thoracic Society/European Respiratory Society statement: standards for the diagnosis and management of individuals with alpha-1 antitrypsin deficiency. Am J Respir Crit Care Med. 2003;168(7):818-900.
4. https://clinicaltrials.gov/ct2/show/NCT04167345.
5. https://clinicaltrials.gov/ct2/show/NCT03679598.
6. https://clinicaltrials.gov/ct2/show/NCT03636347.
7. https://www.vrtx.com/research-development/pipeline/alpha-1-antitrypsin-deficiency/.
8. https://www.mereobiopharma.com/pipeline/mph-966-alvelestat/.
BEST PRACTICES
New Buzz Words in Pulmonary World….. “PIF” and ”PIFR”
Margo Bell RRT, PDE, TTS
Novant Health Forsyth, Pulmonary Disease Navigator
mabell-hughes@novanthealth.org
Anyone that assists in the management of COPD patients understands that their prescribed inhaled medications are vital to best management of their disease. I’ve been introduced to In-CheckTM Dial (Alliance Tech Medical, Granbury, TX). It is a handheld, low-range inspiratory flow device that simulates the resistance of many of the inhaled devices. Its purpose is to validate a COPD patient’s PIFR (Peak Inspiratory Flow Rate) to assure flow rates are optimal for maximum deposition of prescribed inhaled medication. Normal PIFR>=60 L/minute per Loh et al.’s. The In-CheckTM Dial has been scientifically studied and proven reliable +/- 10% and easy for any clinical staff to use. PIFR is the term most often used to describe peak inhalation flow rate, the FDA and pharmaceutical companies use peak PIF.
I believe that future uses of this device could include assessments of all hospitalized patients on ordered inhaled therapy to validate the patient’s inspiratory flow to effectively use what’s prescribed during their hospitalization. This could be completed by a Respiratory Therapist.
Additional use of the In-CheckTM Dial could include use as a teaching/training device to better refine the patient’s ability to use inhaled devices prior to discharge. Consideration should be given to infection control issues as indicated. Fall 2020 NCTS Newsletter
Some studies suggest that approximately 1/3 of patient’s discharged from the hospital after treatment of AECOPD had a PIFR<60L/minute, and are considered suboptimal for DPI therapy.
Ineffective inhalation of medications due to low PIFR can result in poor COPD management and adverse consequences for the patient, and possibly increased readmissions.
1. Loh CH, Peters SP, Lovings TM, and Ohar JA: Suboptimal inspiratory flow rates are associated with
chronic obstructive pulmonary disease and all cause readmissions. Ann AM Thorac Soc.
2017;14:1305-1311.
2. Janssens W, VandenBrande P, Hardeman E, De Langhe E, Philps T, Troosters T, and Decramer M:
Inspiratory flow rates at different levels of resistance in elderly COPD patients. Eur Respir J.
2008;31:8-83.
Is it finally time for a RCT of Therapeutic Plasma Exchange (TPE) for sepsis?
Jason Thomason, MD
Salem Chest Specialists, Winston Salem
The COVID-19 pandemic has forced us to rethink the most effective and efficient delivery of critical care across our state. Targeting the cytokine storm – including the inherent endothelial activation and micro-thrombi formation – has proven difficult. Relatedly, I read with great interest a recently published case report using TPE for a COVID-19 PNA patient suffering from multi system organ failure (MSOF)1. Her rapid and sustained improvement was remarkable, and my enthusiasm for a trial of TPE for sepsis + MSOF was rekindled.
Our single center experience with TPE was recently published in Critical Care as a retrospective, observational chart review2. All patients were suffering from catecholamine-resistant sepsis (≥ 2 vasopressors) and MSOF. Outcomes were compared between 40 treated adult patients versus 40 controls, matching closely for variables such as age, co-morbidities, lactate levels, and severity of illness (APACHE II score > 30, SOFA score ≈ 14). Astoundingly, the 28-day mortality rate was only 40% in the TPE group vs 65% in the “standard care” group (p = 0.043).
The proposed benefits from TPE among this cohort are multifold: reduction in circulating cytokines and inflammatory mediators, restoration of endothelial integrity, and (perhaps most importantly) improvement in the hypercoagulable microcirculatory state. The latter is attenuated by removal of ultra-large von Willebrand factor multimers (ULvWF), ADAMTS-13 inhibitors, and plasminogen activator inhibitor (PAI-1) while restoring ADAMTS-13 activity.
Literature review reveals similar promising results, albeit mostly among case series and case reports. Accordingly, the American Society for Aphaeresis offers a category III, 2B recommendation for the use of TPE in this setting3. No multicenter, randomized controlled trial (RCT) yet exists, even in the world of pediatric critical care which seems to have more firmly embraced this treatment option among select patients. Fall 2020 NCTS Newsletter
While acknowledging the positive results suggested by these observational studies, one must also consider recently failed therapeutics (i.e.; Vitamin C/thiamine/steroids) and contemplate the potential risks inherent to TPE (i.e.; immune modulation, placement of a dialysis style catheter). Weighing all of this carefully and in the words of a former mentor, there certainly seems to be clinical equipoise on the matter. A well-designed, multicenter, RCT remains the only trusted method to elicit a final answer.
As our NCTS network continues to grow in 2021, perhaps we can join together across the state to design and implement such a potentially pivotal trial.
1. Keith et al, SAGE Open Medical Case Reports (2020)Vol 8:1-4
2. Keith et al, Critical Care (2020)24:518
3. Padmanabhan et al, J Clin Apher (2019)34(3):171-354
Officers – North Carolina Thoracic Society
President: James Jas Davidson, MD, FCCP; Asheville, Asheville Pulmonary and Critical Care Associates jamesjasdavidson@gmail.com
Vice President: Mashael Al-Hegelan, MD; Durham, Assistant Professor, Duke University Division of Pulmonary, Allergy, and Critical Care Medicine
Secretary-Treasurer: Praveen Mannam, MD, Greensboro, Cone Health
Chapter Councilor: M. Brad Drummond, MD, MHS; Chapel Hill, Associate Professor, UNC at Chapel Hill
Division of Pulmonary Diseases and Critical Care Medicine
Executive Director – Roy Pleasants, PharmD ncthoracicsociety@gmail.com