We are excited to start the month off with a new #RadiologyRounds
A young adult man in his 20s presents with dyspnea on exertion, productive cough, intermittent wheezing and general fatigue. A chest x-ray was obtained as part of his work-up.
You can identify hyperinflation, interstitial changes and bronchial wall thickening on this image with concern for associated bronchiectasis
You should have Sarcoidosis, Cystic Fibrosis (CF), Hypersensitivity Pneumonitis (HP) and Lymphangioleiomyomatosis (LAM) on the differential
A CT chest is obtained given his abnormal chest x-ray and representative images are shown below
Given upper lobe bronchiectasis you are concerned for cystic fibrosis. A sweat chloride test is obtained and was elevated suggesting CF and further genetic testing was sent to confirm the diagnosis.
We’re back with our Top Consults series to talk about Lung Transplant! This is a topic that every pulmonologist should have background knowledge about since it impacts the care of patients with end-stage lung disease of any cause. We will talk about the indications for referral and transplant, how to advise patients and some unique considerations for evaluation. Enjoy, rate and review us, and share your thoughts about the episode!
Meet Our Guests
Dr. Meghan Aversa is an Assistant Professor of Medicine at the University of Toronto and her expertise involves patients with end stage lung disease and lung transplant.
Dr. Hannah Mannemis an Associate Professor of Medicine at the University of Virginia Health. Hannah joined faculty at UVA in 2016 and she has expertise in ILD and Lung Transplant.
Learning Points
Trends in lung transplant:
Global Increase in Lung Transplants: Over the past three decades, there has been a gradual worldwide increase in lung transplants, with approximately 4,500 performed annually. North America conducts over half of these transplants, and the growth is particularly notable in double lung transplants.
Indications and Disease Trends: Interstitial lung disease (ILD) has seen a significant rise in lung transplant indications, surpassing COPD as the leading cause. ILD, especially idiopathic pulmonary fibrosis (IPF), constitutes a substantial portion (40%) of all transplants. However, the trend is primarily observed in North America.
Decline in Cystic Fibrosis Cases: While Cystic Fibrosis is still a significant indication for lung transplant, its percentage has been declining, likely due to improvements in drugs and CFTR modulators.
Evolution of Lung Transplant Candidates: Over the past five years, lung transplant candidates have become sicker, with higher listing scores and increased hospitalization rates at the time of transplant. More patients have antibodies affecting match difficulty. The average age of patients has increased, with 35% being over 65, a demographic that was previously considered contraindicated.
Impact of COVID-19: The COVID-19 pandemic has influenced lung transplant trends. In 2020, UNOS added COVID-19-related ARDS and pulmonary fibrosis as indications. In 2021, these indications constituted about 10% of lung transplants, making it the third most common indication. Two-thirds were due to COVID-19 ARDS, and one-third due to pulmonary fibrosis. The long-term impact, especially with evolving vaccine dynamics, is still uncertain.
Indications for transplant referral:
ISHLT Consensus Document Update (2021): The ISHLT consensus document for lung transplant candidate selection was updated in 2021. It is available on the ISHLT website and serves as a valuable guideline for pulmonologists considering referrals for lung transplant assessment.
General Rule of Thumb for Chronic Lung Diseases: According to the consensus document, a general rule of thumb for all patients with chronic and stage lung diseases is to consider lung transplant if there is a high (more than 50%) risk of death from the lung disease within the next two years. Prognostic markers vary based on the underlying lung disease.
Disease-Specific Recommendations: The consensus document provides disease-specific recommendations. The key diseases highlighted are COPD, ILD, CF, and PH.
COPD: Referral is recommended when the BODE index is in the range of 5 to 6, with additional factors that increase mortality, such as frequent exacerbations, low FEV1 (20-25%), or rapidly increasing BODE. Referral is also advised for clinically deteriorating patients or those with an unacceptably low quality of life despite maximal medical therapy.
ILD (Particularly IPF): Early referral is suggested, ideally at the time of diagnosis. For any pulmonary fibrosis, referral is recommended if FEC is less than 80% or declining by 10% in two years, or DLCO is less than 40% or declining by 15% in two years. Other factors for referral include radiographic progression or a need for supplemental oxygen.
Cystic Fibrosis (CF): Referral is encouraged for those with FEV1 less than 30%, and even 40% if there’s reduced walk distance, hypercapnia, PH, frequent exacerbations, or rapid decline.
Pulmonary Hypertension (PH): Referral criteria include a REVEAL score of eight, significant RV dysfunction, progressive disease on therapy, need for IV prostacyclin therapy, and specific conditions like PVOD, PCH, scleroderma pulmonary artery aneurysms, which should be referred early due to their rapid progression.
Transplant evaluation process
Phases of Lung Transplant Evaluation:
Referral and Initial Visit: The process begins with a referral, often from a primary pulmonologist. Patients can also self-refer. The initial phase involves insurance authorization and confirming the underlying diagnosis while ensuring all other treatment options are exhausted.
Assessment of Disease Severity: The severity of end-stage lung disease is assessed to determine the timing of the workup, which varies depending on the patient’s condition and the center’s protocols.
Diagnostic Steps: A thorough diagnostic workup follows the initial visit, including various tests, imaging, and meetings with multidisciplinary teams to assess medical and social factors influencing transplant success.
Follow-Up Appointments: Patients typically have multiple follow-up appointments to track the evolution of the disease and ensure health maintenance and vaccinations are up to date.
Selection Committee: The final phase involves a selection committee that determines if the patient is a candidate. If so, there may be conditional requirements before officially listing the patient.
Multidisciplinary Approach: Lung transplant evaluation involves collaboration with various specialists, including social work, finance, nutrition, pharmacy, physical therapy, and potentially other consult services. The efficiency of this process is optimized for both the patient and the medical team.
Diagnostic Workup:
Medical Testing: Involves blood work, cardiac testing (echo, left and right heart cath), and imaging, including abdominal imaging, VQ scans, DEXA scans, and 24-hour urine analysis.
Multidisciplinary Meetings: Patients meet with members of the multidisciplinary team, addressing medical comorbidities as well as social and psychological factors.
Follow-Up Appointments: Multiple appointments allow for tracking disease progression and ensuring overall health maintenance.
Selection Committee Decision: The patient receives a decision from the selection committee, determining candidacy. Sometimes, patients are considered candidates with conditions (e.g., completing vaccinations or losing weight). Timing of listing is also discussed to ensure optimal candidacy.
Patient Involvement: Patients play an active role, and the process may involve self-referral, understanding and completing requirements, and active participation in follow-up appointments.
Efficiency and Individualization: The evaluation process is tailored to the patient’s condition, and centers aim to efficiently organize diagnostic workup and multidisciplinary meetings to optimize patient care.
Timing of transplant listing for candidates
COPD Patients: For COPD patients, listing is likely when the Bode index is around 7, the FEV1 is under 20%, there is at least moderate pulmonary hypertension (PH), chronic hypercapnia, or severe exacerbations.
ILD Patients: Patients with interstitial lung disease (ILD) are likely to be listed when showing signs of progression or decline in forced expiratory capacity (FEC), diffusing capacity of the lungs for carbon monoxide (DLCO), or six-minute walk distance. Other indicators include hypoxemia, secondary pulmonary hypertension, or hospitalization for complications.
CF Patients: Cystic fibrosis (CF) patients are considered for listing when FEV1 is below 25% or is rapidly declining, and if they experience frequent hospitalizations. Listing criteria also include the presence of pulmonary hypertension, chronic hypoxemia, or hypercapnia.
Pulmonary Hypertension Patients: Those with primary pulmonary hypertension may be listed when the reveal score is above 10 on intravenous therapy, there is progressive hypoxemia, or if there are renal or liver dysfunctions associated with pulmonary hypertension (PH).
Changes from the LAS system to the CAS system
Transition to Composite Allocation Score (CAS):
Background and Timing: In March 2023, the lung allocation system (LAS) transitioned to the composite allocation score (CAS), a major change in the allocation of lung transplants.
Reasoning Behind the Change: The change aimed to improve organ matching, prioritize sick candidates, enhance long-term survival, promote equity, increase transplant opportunities for specific patient groups (especially pediatric patients), and manage geographical variation in organ placement.
Components of CAS:
Medical Urgency: Based on waitlist mortality at one year without a transplant and the likelihood of survival post-transplant, now assessed at greater than five years, with equal weighting.
Recipient Variables: Includes factors like height discrepancy, blood type matching, sensitization (immune system matching), and other recipient variations.
Candidate Biology: Focuses on pediatric patients (less than 18 years old) and individuals are a prior living donor.
Donor Variables: Addresses donor characteristics, emphasizing proximity and travel distance from the organ hospital.
Early Data and Observations: The initial three-month monitoring period has shown changes in O blood type scores, prompting adjustments. Notable outcomes include a 16% increase in the number of lung transplants, a decrease in waitlist deaths and removals, and changes in median distance between donor hospital and transplant center.
Exception Scores: The number of exception scores has increased, allowing for adjustments when the assigned score may not reflect the patient’s true medical urgency.
Caution and Early Analysis: Early data, while promising, is subject to caution as centers were aware of the upcoming change. The impact on different age groups and the reasons for exceptions are being closely monitored and may evolve as more data becomes available.
Ongoing Monitoring and Potential Evolution: The data is being closely tracked by medical directors, and further changes to the scoring system may occur based on ongoing analysis and experience with the CAS. The impact on patient outcomes and allocation efficiency will continue to be studied and refined.
Advising patients on what to expect in terms of prognosis and survival after lung transplant
Survival Statistics:
Overall three is approximately 50 percent survival at five years, and the median survival time is approximately six and a half years.
Significant variations based on factors such as diagnosis, age, and comorbidities.
Survival outcomes differ for specific groups, e.g., cystic fibrosis (CF) patients, those older than 65, and individuals with interstitial lung disease (ILD).
Quality of Life Emphasis:
Shift in focus from survival alone to the patient’s goals and quality of life.
Highlighting the importance of understanding and aligning with the patient’s individual quality of life expectations.
Investment in Healthcare Team and Lifestyle Change:
Emphasis on the long-term commitment and involvement with the healthcare team post-transplant.
A substantial investment in healthcare post-transplant, including regular visits, extensive blood work, and medication management.
Cultural shift for patients to adapt to a new routine of frequent medical visits even when otherwise healthy.
Complications and Side Effects:
Acknowledgment of potential complications within the first year, making the initial post-transplant period a full-time job.
Discussion of various complications and medication side effects, ensuring patients are informed.
Multidisciplinary approach involving nutritionists, physical therapists, and other specialists to address complications and enhance the patient’s quality of life.
Individualized Patient Approach:
Recognition of the patient’s fight, spirit, and motivation as crucial factors for successful transplantation.
Encouraging patients to set goals for their post-transplant life.
Ethical considerations regarding transplanting older patients, with the importance of assessing overall well-being, motivation, and mental health.
Acknowledgment of Averages and Unpredictability:
Communication of averages, but a reminder of the inherent unpredictability in the post-transplant course.
Preparing patients for potential complications and the need to adapt to unforeseen challenges.
Managing expectations by highlighting the unpredictability of individual transplant journeys.
Quality of Life Improvement:
Despite complications and side effects, lung transplant often results in a significant improvement in the patient’s quality of life.
Patients generally experience increased satisfaction and happiness post-transplant, outweighing the challenges associated with the procedure and subsequent care.
We are extremely excited to introduce our new Pulm PEEPs Meet the Patients series. Teaching and learning medicine is an incredible journey, and the goal is always to be improving patient care. Patients are our best teachers about the diseases we encounter, so the goal of this series is to spend more time with patients with pulmonary disease and with those who have been critically ill. For our first episode, we are thrilled to be joined by Katie Fielding.
Katie s an educator and spent 13 years teaching high school science. She now specializes in integrating technology into the classroom to enhance education. Katie was diagnosed with CF as an infant and has spent years as a patient advocate. She works closely with the Cystic Fibrosis Foundation and serves on the Adult Advocacy Council.
Katie gives us an incredible perspective about what it is like to live with Cystic Fibrosis, how her life has changed with modern therapies, and how to be the best provider possible.
The Pulm PEEPs are joined again by Natalie West to discuss a patient who presented with a chronic, productive cough. Listen in today as we work through our differential diagnosis, interpret basic pulmonary testing, and share our clinical reasoning along the way. We have some fantastic diagnostic and treatment teaching points, so once you’ve solved the case check out the takeaways and infographics below. Please let us know any additional insights you have on Twitter!
Patient Presentation
A 50-year-old woman, who is a never smoker, with a past medical history of recurrent pancreatitis presents to the pulmonary clinic with a chronic, productive cough. Her cough has been present for 3 years and has increased in frequency to now being present daily. In the last three months, the cough has also worsened and is productive of small amounts of yellow to green sputum. She has a history of chronic post-nasal drip and sinus infections, and uses intranasal steroids, but has not noted changes in these symptoms. There is no significant family history of pulmonary disease, and an exposure history review of symptoms is negative.
On physical exam, she was a thin woman who appeared her stated age and was breathing comfortably on room air. Her exam was notable for mild expiratory wheezing, primarily on auscultation of the right posterior lung field. She had no cyanosis, clubbing, evidence of volume overload, or abdominal tenderness.
Basic Spirometry Values
Chest X-ray
Representative Images from CT Scan
Key Learning Points
**Spoilers Ahead** If you want to think through the case on your own we advise listening to the episode first before looking at the infographics below.
Differential Diagnosis of Chronic Cough
Three most common causes: upper airway cough syndrome, GERD, cough variant asthma
Additional etiologies to consider: chronic bronchitis, post-infectious after a respiratory tract infection, bronchiectasis, ACE inhibitors, lung cancer, eosinophilic bronchitis, interstitial lung disease
Imaging Pearl
Evaluating Bronchiectasis
Making a New Diagnosis of Cystic Fibrosis in an Adult
Sweat testing
Sweat testing should be done in CF accredited center. Inform patients that there are no needles involved. Pilocarpine and electrical stimulation are applied to the arm or leg to stimulate the sweat gland, and then sweat is collected on filter paper, a gauze, or a plastic coil. From there, the amount of chloride in the sweat is calculated
Results
< 30 normal
31 – 60 indeterminate
> 60 is positive and Cystic Fibrosis is likely
What do you do with an Indeterminate test?
Patients with milder phenotypes of Cystic Fibrosis can have a normal or indeterminate sweat chloride level, and 10% of adults diagnosed with CF have a normal sweat chloride. If the sweat chloride test is indeterminate or normal, but suspicion is high for CF, then genetic testing for the whole array of mutations should be performed
Pulm PEEPs hosts, Kristina Montemayor and David Furfaro, bring our first episode in our Top Consults series. In this series, we will bring in experts to work through the most common pulmonary and critical care consults. Whether you are the consulting physician, or a pulmonologist responding to the page, these episodes are geared to give you all the information you need to care for your patients!
Today, we are joined by Chris Kapp and Matthew Schimmel, two interventional pulmonologists, to discuss hemoptysis. Chris and Matt will help us work through two hemoptysis consults, and together we’ll provide a framework for thinking about hemoptysis, outline some key components of the evaluation, and delve into treatment options.
Key Learning Points
Hemoptysis Evaluation
Hemoptysis Management
Life-Threatening or Large Volume Hemoptysis
Stabilize the patient! Make sure the airway is protected either by the patient coughing themselves, or intubation if needed. Provide hemodynamic support with IVF, blood products, and pressors if needed. If it is known which lung has the bleeding the patient can be positioned so the lung with the bleeding is down. This protects the non-bleeding lung.
Correct any bleeding diathesis If the patient is on anti-coagulation, or has any reversible bleeding diathesis, these should be corrected immediately to reduce further bleeding.
Localize the bleed If the patient is stable, they should undergo a CTA to localize the bleeding. If they are not stable to make it to a CT scan, a bronchoscopy should be performed.
Bronchoscopic treatment In addition to clearing blood from the airway, bronchoscopy can localize the bleeding. With available expertise, bronchoscopic treatments can be performed such as ice saline, topical epinephrine, or balloon tamponade to isolate the bleed.
Definitive therapy with arteriography and embolization Patients with life-threatening hemoptysis should ultimately undergo arteriography and embolization of any bleeding vessel. If this is not possible, then surgery can be needed in some cases.
A note on diffuse hemoptysis If there is not one distinct bleeding lesion, then localizing and treating the bleed becomes more difficult. For diffuse alveolar hemorrhage, evaluation should be performed for if it is primary, and due to an immunologic cause and capillaritis, or secondary to a systemic disease and / or bleeding diathesis. These investigations will guide available treatment options. Capillaritis from an immunologic cause, such as lupus or vasculitis, can be treated with systemic glucocorticoids and an additional immunosuppressive agent such as cyclophosphamide or rituximab.
Non-life-threatening or Small Volume Hemoptysis
Monitor for clinical worsening Patient’s should be monitored, either in the in-patient or out-patient setting, for increased volume or frequency of hemoptysis and for any clinical worsening, such as desaturations or decreased ability to clear the airway.
Correct any bleeding diathesis If the patient is on anti-coagulation, or has any reversible bleeding diathesis, these should be corrected immediately to reduce further bleeding. In pattients with non-life-threateneing hemoptysis this requires careful consideration of balancing the risk of bleeding vs the benefits for continuing anti-coagulation.
Evaluate for underlying cause Patient’s should undergo imaging and evaluation for the underlying cause of the hemoptysis. This may be evidence of an underlying infection, a pulmonary embolism, or new lung lesions making the patient at risk. If the source can’t be found on non-invasive imaging, and there is no clear systemic source such as an infection, a bronchoscopy is warranted. Any underlying cause should be treated and investigated further.
Inhaled Tranexamic Acid Nebulized tranexamic acid is well tolerated and can help resolve hemopytysis without invasive procedures.
The Pulm PEEPs (Kristina Montemayor and Dave Furfaro) host a panel of Cystic Fibrosis (CF) providers to discuss the current state of the disease, recent advances in cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapies, and the evolving faces and voices of Cystic Fibrosis.
Cystic Fibrosis is an autosomal recessive disorder caused by mutations in the CFTR gene that affects over 30,000 individuals in the United States and 70,000 people worldwide. Absence or dysfunction of the CFTR protein leads to abnormal secretion of mucus, sweat, and digestive fluids, which impacts the lungs, digestive tract, and reproductive system.
From the first formal publication on Cystic Fibrosis in 1938 by Dorothy Hansine Andersen, to the discovery of the delta F508 mutation and CFTR gene in 1988 -1989 by Lap-Chee Tsui, Francis Collins, and John R. Riordan, to the approval of the first CFTR modulator therapy, Ivacaftor, in 2012, our knowledge about Cystic FIbrosis has been advancing in leaps and bounds. As therapies have improved, they have dramatically impacted the lives of patients with Cystic Fibrosis. Join us today as we explore what this evolution in care has looked like from the perspective of Cystic Fibrosis providers, and hear about the new questions and challenges on the horizon.
Meet our guests
Emily DiMango is a Professor of Medicine at Columbia University Medical Center and the Director of the John Edsall-John Wood Asthma Center and the Gunnar Esiason Adult Cystic Fibrosis Program
Terri Laguna is an Associate Professor of Pediatrics at Northwestern Medicine / Feinberg School of Medicine and the Chief of Pulmonary and Sleep Medicine in the Department of Pediatrics
Patrick Sosnay is a Senior Medical Director at Vertex Pharmaceuticals and specializes in Cystic Fibrosis
Natalie West is an Assistant Professor of Medicine at Johns Hopkins Hospital and specializes in Cystic Fibrosis.
