46 AJTCCM VOL. 29 NO. 2 2023
EDITORIAL
Interstitial lung diseases (ILD) have over the past 80 years undergone
a multitude of changes in naming conventions, clinical descriptions,
pathological classications, and therapeutic approaches.[1,2] Recent
publications from the ATS/ERS and additionally, the Fleischner
Society, have grouped the diuse parenchymal lung diseases into
various categories based on shared aetiology, histological and/or
radiological pattern and associations with exposures or underlying
rheumatological diseases.[3] Despite these consensus statements,
there remain calls to abandon much of the nomenclature in terms of
naming and focus on other aspects and ways of ‘cohorting’ patients
with interstitial lung disease.[4,5]
e priorities for sorting/classifying/grouping ILDs have varied
from: ‘what to call it’ such as CFA or IPF, ‘what it looks like’ such as
UIP or NSIP, and more recently ‘how it behaves’ such as progressive
pulmonary brosis. ese priorities have been driven by the evolving
understanding of pathophysiology, radiology, clinical course, and
responses to newer therapies. For example, the big drive away from
oral steroids for IPF arose from the Panther trial data,[6] and the focus
on IPF treatment with antibrotics aer the INPULSIS, CAPACITY
and ASCEND trials.[7-9] More recently the treatment focus has been
on ‘progressive pulmonary brosis’; regardless of original grouping/
classication, focussing on ‘behaviour’ based on results from the
INBUILD trial.[10]
erefore, in answer to the question: “does it matter what we call
you, or what you look like, or how you behave?” e answer is yes:
e current focus on behaviour is predicated on an understanding of
what the underlying disease is and how it generally behaves, or at least
predicted to behave. Not all interstitial lung diseases progress at the
same rate, even those classied as progressive pulmonary brosis. is
has signicant impact on planning for end-of-life care and planning
for lung transplantation. Furthermore, the name we give something
has implications[5] – not only for the patient (e.g., life expectancy
with a label of IPF or RA-ILD), but also funders who will only pay
for certain medications for certain conditions, as well as colleagues
(rheumatology, dermatology) who may need to consult and care for
the patient. And nally – what you are going to call the ‘disease’ in your
manuscript or research grant proposal.
Athol Wells and colleagues[5] wrote a perspective paper in 2018 on
thoughts around changing the name of IPF, and cited arguments from
various quarters about why this should or should not happen. One
of the key points made (quoting William James) which is relevant to
the “name-appearance-or-behaviour” argument, is that ‘classications
merely serve the purpose they serve’.[5] IPF or not, equals treatment
with an antibrotic or not; progressive brosis or not, equals treatment
with nintedanib or not. is dichotomous approach currently runs
the risk of distilling a vast array of varying complex clinical entities
with varying complex manifestations into a single common pathway
of brosis or not. is “reductionist” approach to management of
respiratory disease is dual-edged. A single inhaler for both asthma
and COPD, diseases divided into steroid responsive or not etc. belies
the unique and complex nature of each of the conditions. e corollary
is that this approach (for ILD) does simplify the treatment choices for
clinicians who do not have ready access to surgical lung biopsies and
more importantly, multi-disciplinary team (MDT) meetings to settle
on diagnoses.
Fibrotic lung diseases have been the focus of several perspective
articles in high impact journals given the dramatic responses to
antibrotics in recent trials of so called ‘progressive pulmonary brosis’,
which still has no validated diagnostic criteria.[3,10] e temptation
therefore, is for the clinician to ignore the ‘name’ and just focus on
the ‘behaviour’. Ultimately like the adage ‘all bleeding eventually stops’,
‘most chronic respiratory conditions end with brosis’ to a degree also
holds true. e challenge however, is to dierentiate the deterioration
induced by active inflammation and that by active fibrosis, to
correctly manage the underlying pathogenic process. e alternative
is just to ‘treat both’ which in the era of precision medicine seems
a step backwards, which Wuyts, George and colleagues elegantly
contextualize in their recent opinion pieces.[11]
What has been given little attention in the current IPF ‘name-
appearance-or-behaviour’ discussions, is the fact that when
respiratory failure is imminent, name becomes important. The
diagnosis/original label takes on a much greater signicance when
“slowing progression” has failed or is ‘failing’: IPF, is known to
have a median survival of 3 - 5 years postdiagnosis, CTD-ILD is
known to have a less dramatic progression but with systemic/joint
complications, and Scleroderma associated-ILD is known to have
signicant obstacles to lung transplant, despite all potentially being
lumped into a ‘progressive brosis’ bucket. Not only does ‘What
we call you’ become of major importance but also ‘how we treated
you’, and not only what are you receiving - an antibrotic currently
based on your recent ‘behaviour’. is is particularly of importance
in resource-limited settings: the dierential cost of oral prednisone
compared to an antibrotic is enormous, HRCT scans are not freely
available especially in follow up, and specialist resources such as
MDT’s are few and far between. erefore, the temptation to default
to oral prednisone, as there is little else to oer needs to be oset
with the regulatory/funding ght to gain access to an antibrotic
for a specic patient.
Lung transplantation remains the nal potential option in patients
with end stage lung disease, is highly dependent on the underlying
disease and any complications of treatment: scleroderma patients have
specic risks associated with cardiac and oesophageal dysfunction that
can impact on outcomes and may even preclude transplant;[12] steroid-
induced obesity, diabetes and or osteoporosis from chronic steroids for
sarcoidosis or COPD for example can complicate transplant patient
care.[13,14] Connective tissue disease-associated ILD may complicate
transplant by the nature of the underlying disease and the presence of
antibodies increasing risk of rejection.[15,16]
It is therefore critical to ‘label’ our patients correctly, both for their
acute management strategy, but also for their long-term management
strategy. ankfully the days of high dose steroids for IPF are over, but
steroids are commonly used in many other interstitial lung diseases
Interstitial lung disease: Does it matter what we call you, or what
you look like, or how you behave?
AJTCCM VOL. 29 NO. 2 2023 47
EDITORIAL
such as sarcoid, NSIP, COP etc. – to very good eect, and only when
intolerant or ineective, are changes to other modalities of therapy
considered. Not that any immunomodulatory /immunosuppressive
therapy is without risk, managing the acute illness oen rightly or
wrongly takes precedence over managing the chronic. Steroid-induced
diabetes/osteoporosis no matter how you look at it – has long term
implications, especially for lung transplantation.
Our goal as clinicians must be to keep the ‘name-appearance-
behaviour’ conundrum in balance as we care for patients with complex
lung disease, varied underlying aetiologies and options for long term
therapy. In low-resourced settings particularly, labelling takes on
a dierent guise, as access to antibrotics ‘for all’ is simply not an
option and making dicult choices to not treat (with oral steroids),
is challenging.
Focusing only on the behaviour belies the importance of the
underlying condition both in the short and long term. Focusing only
on the appearance may reassure us or blind us from a progressive
behaviour. It may even cause us to persist with toxic and damaging
therapy. Focusing only on label misses the point that there is a patient
behind the FVC and that we at best slow down the progression, and
when there is no FVC le, a person with a name remains.
Richard van Zyl-Smit, MB ChB, FRCP(UK), Dip HIV(Man),
MMED, FCP(SA), Cert Pulm(SA), PhD, ATSF
Division of Pulmonology and Department of Medicine, University of
CapeTown and Groote Schuur Hospital, Cape Town, South Africa
richard.vanzyl-smit@uct.ac.za
Gurveen Soin, MBChB (UON), MMed (Int), FCP (SA)
Division of Rheumatology, Department of Medicine, Stellenbosch
University, Tygerberg Hospital, Cape Town, South Africa
Greg Calligaro, BSc Hons, MB BCh, Dip PEC (SA), MMed (Int),
FCP (SA), Cert Pulm (SA)
Division of Pulmonology, Department of Medicine, Groote Schuur
Hospital, Cape Town, South Africa
1. Raghu G. Idiopathic pulmonary brosis: lessons from clinical trials over the past 25
years. Eur Respir J 2017;50(4). https://doi.org/10.1183/13993003.01209-2017
2. Martinez FJ, Collard HR, Pardo A, etal. Idiopathic pulmonary brosis. Nat Rev Dis
Primers 2017;3:17074. https://doi.org/10.1038/nrdp.2017.74
3. Raghu G, Remy-Jardin M, Richeldi L, etal. Idiopathic pulmonary brosis (an
update) and progressive pulmonary brosis in adults: An Ocial ATS/ERS/JRS/
ALAT Clinical Practice Guideline. Am J Respir Crit Care Med 2022;205(9):e18-e47.
https://doi.org/10.1164/rccm.202202-0399st
4. Wolters PJ, Blackwell TS, Eickelberg O, etal. Time for a change: is idiopathic
pulmonary fibrosis still idiopathic and only fibrotic? Lancet Respir Med
2018;6(2):154-160.
5. Wells AU, Brown KK, Flaherty KR, Kolb M, annickal VJ, Group IPFCW. What’s in
a name? at which we call IPF, by any other name would act the same. Eur Respir
J 2018;51(5). https://doi.org/10.1183/13993003.00692-2018
6. The Idiopathic Pulmonary Fibrosis Clinical Research Network. Prednisone,
azathioprine, and n-acetylcysteine for pulmonary fibrosis. N Eng J Med
2012;366(21):1968-1977. https://doi.org/10.1056/nejmoa1113354
7. Noble PW, Albera C, Bradford WZ, et al. Pirfenidone in patients with
idiopathic pulmonary fibrosis (CAPACITY): two randomised trials. Lancet
2011;377(9779):1760-1769. https://doi.org/10.1016/s0140-6736(11)60405-4
8. King TE, Bradford WZ, Castro-Bernardini S, etal. A phase 3 trial of pirfenidone in
patients with idiopathic pulmonary brosis. N Eng J Med 2014;370(22):2083-2092.
https://doi.org/10.1056/nejmoa1402582
9. Richeldi L, du Bois RM, Raghu G, etal. Efficacy and safety of nintedanib in
idiopathic pulmonary brosis. N Eng J Med 2014;370(22):2071-2082. https://doi.
org/10.1056/nejmoa1402584
10. Flaherty KR, Wells AU, Cottin V, etal. Nintedanib in progressive brosing interstitial
lung diseases. N Engl J Med 2019;381(18):1718-1727.
11. Wuyts WA, Wijsenbeek M, Bondue B, etal. Idiopathic pulmonary brosis: Best
practice in monitoring and managing a relentless brotic disease. Respiration
2020;99(1):73-82. https://doi.org/10.1159/000504763
12. Khan IY, Singer LG, de Perrot M, etal. Survival aer lung transplantation in systemic
sclerosis. A systematic review. Respir Med 2013;107(12):2081-2087. https://doi.
org/10.1016/j.rmed.2013.09.015
13. Shane E, Silverberg SJ, Donovan D, etal. Osteoporosis in lung transplantation
candidates with end-stage pulmonary disease. Am J Med 1996;101(3):262-269.
https://doi.org/10.1016/s0002-9343(96)00155-6
14. Mora Cuesta VM, Iturbe Fernandez D, Gallardo Agromayor E, etal. Osteoporosis in
lung transplant patients. European Resp J 2014;44(Suppl 58):P2456.
15. McQuiston A, Emtiazjoo A, Angel P, Machuca T, Christie J, Atkinson C. Set up
for failure: pre-existing autoantibodies in lung transplant. Front Immunol 2021;12.
https://doi.org/10.3389%2Fmmu.2021.711102
16. Yazdani A, Singer LG, Strand V, Gelber AC, Williams L, Mittoo S. Survival and
quality of life in rheumatoid arthritis-associated interstitial lung disease after
lung transplantation. J Heart Lung Transplant 2014;33(5):514-520. https://doi.
org/10.1016/j.healun.2014.01.858
Afr J Thoracic Crit Care Med 2023;29(2):e803. https://doi.
org/10.7196/AJTCCM.2023.v29i2.803
