Last week in Pulmonary Report, we talked about a case of isolated mediastinal/hilar adenopathy (IMHL). 4 important differential considerations were discussed:
We discussed several studies that evaluated the optimal evaluation for suspicious IMHL, as well as factors which were shown retrospectively to be suggestive of reactive adenopathy.
This week in Pulmonary Report, Dr. Ludwig presented the case of a 68 year old man with chronic exertional dyspnea and abnormal PFTs. Her evaluation (which is still ongoing!) tackled a a high-yield and challenging topic – what happens when your patient has restrictive PFTs but doesn’t have parenchymal disease to explain it?
The broad categories of restrictive lung disease can be remembered with the mnemonic PAINT:
In our patient’s case, an HRCT was performed and did not reveal clear parenchymal/pleural causes of restriction, leading us down the “extra-parenchymal” pathway:
Slide: extra-parenchymal causes of restrictive lung dz
Several maneuvers are available to aid in the differential diagnosis of a restrictive PFT
Supine and upright VC may suggest neuromuscular causes of restrictive lung disease.
Chest wall and diaphragm mechanics
MVV (or maximal voluntary ventilation) wherein patients are asked to take rapid deep breaths for 12 seconds, is demonstrated in the video below:
MVVpred = FEV1 x ~35-40 (lower values suggestive of neuromuscular weakness)
Maximum inspiratory/expiratory pressure (MIP and MEP) are also decreased in neuromuscular disease:
Pre (upright) and post (supine) flow-volume loop
Pre (upright) and post (supine) vital capacity
MIP and MEP
Diaphragm function may also be evaluated using other modalities:
Diaphragm ultrasound for excursion and fractional thickening
Obtaining a diaphragmatic ultrasound
Thickening fraction: [(thickness at end-inspiration—thickness at end-expiration)/thickness at end-expiration]. <20% is indicative of diaphragmatic weakness
Normal diaphragm excursion: 6cm (female) 7cm (male) during deep breathing
Electromyography of diaphragm to assess for innervation
Fluoroscopic sniff test can be used to detect unilateral pathology
Finally, some management considerations for respiratory symptoms in the patient with neuromuscular disease:
Consider blood gas testing for hypercapnia when FVC <40% pred
Thanks Amy!
It’s been awhile since our last ILD round-up, but we are glad to be back in action! This week we talked about a young man with CVID, ITP and persistent groundglass opacities. We discussed a concern for granulomatous and lymphocytic interstitial lung disease (GL-ILD)
I. What is GL-ILD?
Seen in patients with CVID. With the advent of effective therapies (namely IVIG), increased prevalence of non-infectious complications of CVID (non-infectious complications now seen in 70% of patients with CVID).
GL-ILD is seen in 8-20% of cases of CVID, making it the most common ILD in this condition. It may also be seen in CTLA-4 deficiency. Associated with splenomegaly, immune-mediated cytopenias, and ITP. BAL demonstrates increased percentage of CD21lo B cells. Pathology demonstrates a peribronchiolar lymphocytic infiltrate, usually associated with granulomas (94% in one case series) and often with organization.
Image: peribronchial and interstitial lymphocytic infiltration
Image: Epithelioid granuloma
II. What are the characteristic HRCT findings of GL-ILD?
Solid & subsolid nodules, groundglass opacities, reticulations, mediastinal and hilar adenopathy. Less likely to contain reticulation, TBE, honeycombing, masses or consolidation. A radiologic DDX includes infection, organizing pneumonia, LIP, sarcoidosis and lymphoma. As alreadt noted, splenomegaly (bottom image) is common.
III. How is GL-ILD treated?
Consensus guidelines with strong agreement that mainstay of therapy is optimization of IVIG therapy. Whether to proactively treat or enter active surveillance after IVIG optimization is less well established, nor is whether antibiotic prophylaxis (as is often the case in CVID) is warranted. Corticosteroids are frequently used, but without clear evidence basis or consensus. Potential second line agents include azathioprine, rituximab, MMF.
Sources:
Thanks to Dr. Rowe for a great morning report case – a middle aged man with well-controlled HIV, ESRD on HD, referred to clinic for an abnormal CT as part of pre-transplant workup.
CT with some moderate subcarinal and right paratracheal lymphadenopathy, minimal parenchymal findings.
What next?
Differential:
EBUS to the rescue! – REMEDY: AJRCCM 2012 study showed that EBUS mediastinoscopies in 87% of cases – 67/77 cases were diagnosed with EBUS; of the 10 undiagnosed, only 6 got diagnoses in mediastinoscopy
Thanks, Tim!
Timothy Rowe, MD, Pulmonary and Critical Care
This week, second-year fellow Elen Gusman presented a case of non-expanding lung (NEL) which presented as a post-thoracentesis hydropneumothorax. Ouch!
Representative clip of a right-sided hydropneumothorax
What are 3 causes of NEL?
What is trapped lung?
When to suspect trapped lung?
How do we diagnose?
Below is a YouTube video walking through three commonly utilized methods of transducing pleural pressure:
Lung ultrasound (LUS) may also predict trapped lung with an absent “sinusoid sign”
How to obtain:
How to distinguish trapped lung from lung entrapment?
StatPearls 2022 “Trapped Lung” (link)
Annals ATS 2019;16(4):506-508. (link)
Semin Respir Crit Care Med 2001;22(6):631-6. (link)
I. A patient with prior clinical diagnosis of pulmonary sarcoidosis presented to care at NMH with progressive pulmonary fibrosis. A transbronchial biopsy with EBUS was performed. The radiographic pattern and biopsy results were thought to be inconsistent with sarcoidosis; a differential of indeterminate UIP v NSIP (idiopathic v IPAF) remained. We discussed sending the patient for Envisia testing.
What do we mean when we say “Envisia”?
Envisia was validated in the BRAVE (Bronchial Sample Collection for a Novel Genomic Test) studies
How well can Envisia distinguish UIP from other pathology in conventional TBBx?
Liu et al. BMJ 2022;377:e066354 https://doi.org/10.1136/bmj-2021-066354
Raghu et al. Lancet Respir Med 2019; 7: 487–96 10.1016/S2213-2600(19)30059-1
II. A patient who is undergoing evaluation for transplant had chronic hypersensitivity pneumonitis (cHP) in his differential diagnosis. We discussed the predictive value of BAL lymphocyte count given the fibrotic/chronic nature of his disease
What is the predictive value of BAL lymphocytosis in cHP?
Today’s morning report featured a fascinating case of eosinophilic pleural effusion from second year fellow Ted Cybulski
Second year PCCM fellow Ted Cybulski | http://tedc.cc/ | Twitter: @tdwck
First thing’s first – how do we define pleural fluid eosinophilia (PFE), and what are classic associations to be familiar with?
Some more quick facts:
Here a closer look at the broad categories on the differential diagnosis of PFE:
In our discussion, Dr. Sporn added that pleural fluid protein <4 and effusion size >1/3 hemithorax are suggestive against tuberculous effusion. A couple of other important points about TB effusion:
Below Ted details the association of eosinophil count in PFE with malignancy – while a lower count (<40%) is MC in malignancy, a higher count is not necessarily reassuring. Other characteristics which carry higher risk for malignant effusion include advanced age and higher pleural fluid LDH (cutoff >900 suggested)
Takeaways
Thanks for leading a great discussion, Ted!
Sources cited
I. A 62 yo female with family history of pulmonary fibrosis with an NSIP pattern
What is the relationship between telomere length and familial pulmonary fibrosis?
-Heterozygous mutations in coding regions of two telomerase genes (TERT :: protein component, TERC :: RNA component) have been associated (found in 15% of kindreds) with familial IPF
Pulmonary fibrosis is seen in 50% of women and 60% of men 60 years and older with TERT mutations
-UIP radiograph pattern (74% HRCT) and UIP pathologic pattern (86% surgical lung biopsy) is most commonly encountered
-Even in sporadic cases of IPF, a significantly higher proportion of individuals have telomere lengths <10th percentile compared with controls, even absent TERT/TERC mutations (present in 1-3% of sporadic cases)
Plotting mean telomere length against age with 10-90th percentile in normal controls mapped in blue region
https://www.atsjournals.org/doi/pdf/10.1164/rccm.200804-550OC
https://doi.org/10.1371/journal.pone.0010680
II. 69 yo F with seropositive RA and progressive fibrosing ILD, found to have upper zone predominant fibrosis, honeycombing, TBE.
What HRCT & histopathologic patterns are most commonly associated with RA-ILD?
-UIP pattern on HRCT most commonly encountered, between 40-60% of cases.
-Histopathology usually correlates with HRCT. MC encountered histopathologic patterns are UIP, NSIP, OP
Aggregated data from multiple studies demonstrating the most common histopathologic patterns in CTD-ILDs. Note larger proportion of UIP in RA-ILD
-RA-ILD associated with UIP pattern has an increased risk of disease progression and death, and increased risk of flares compared with RA-ILD with NSIP pattern
Kaplan-Meier curve showing RA-ILD with UIP pattern; cumulative survival intermediate between RA-ILD with NSIP and IPF (another ILD characterized by UIP HRCT and histopath)
What is the role of antifibrotic therapy in non-IPF ILD?
– A recent trial (INBUILD – 2019) looked at nintedanib (antifibrotic FDA approved for IPF) in patients with non-IPF fibrosing interstitial lung disease (n=663) over 12 months of follow-up
Figure demonstrating the primary endpoint, decline in FVC over period of followup (188 mL in placebo versus 80 mL in nintedanib group).
-As a secondary endpoint, mortality was less in intervention group (11.5% placebo vs 8.1% nintedanib) although this was not statistically significant
– Since publication of INBUILD trial, FDA has approved use of nintedanib/Ofev for non-IPF progressive fibrosing ILDs
Finally, for a current and comprehensive review of the treatment of fibrosing interstitial lung disease including IPF and other progressive pulmonary fibrosis (PPF), make sure to check out a recent review in BMJ by our very own Gabby Liu, Scott Budinger and Jane Dematte!
An algorithmic approach to diagnosis and management
https://doi.org/10.1378/chest.09-0444
https://www.nejm.org/doi/full/10.1056/NEJMoa1908681
https://www.bmj.com/content/377/bmj-2021-066354
Thanks, Tom Bolig, for presenting on idiopathic inflammatory myopathy-associated ILD, focusing on anti-MDA5 ILD.
My takeaways:
Thanks, Tom!
