It has always miffed me how a baby so young as one of our preterm infants can have something “chronic.” This happens far too often when we witness preterm infants get the terrible lung disease we now call chronic lung disease, or CLD.
Other names in use include bronchopulmonary dysplasia, or BPD, which is a more quizzical name and originally derived from a pathologic diagnosis. The other name that seems to be creeping in use is “CLD of prematurity,” but this does not abide by our unwritten rule in neonatology to name conditions with three letter acronyms.
The term “chronic lung disease” is such a diffuse term. I don’t like this name because it is scary to many parents. Their child, often the size of an adult hand, suddenly gets hit with a labeled diagnosis of something chronic. Most associate “chronic” with old and decrepit.
“Chronic” can mean forever.
In medicine we often throw around lots of short form terms. Neonatal caregivers are particularly enamored with acronyms. Is this our obsessive-compulsive nature, or are there so many different problems that we simply had to contract this with an assortment of acronyms? Maybe it’s both. We have IVH, RDS, NEC, BPD/CLD, AOP, OOP, SIP, LOS, EOS… The list goes on.
What if they had something in common?
We’ve tried hard to define CLD to better study it for research and track it for quality purposes, but what we really need is a better clinical definition that captures the lung disease that requires respiratory support after treatment settles for respiratory distress syndrome (RDS).
Waiting until 36 weeks for O2 dependency or respiratory support until we can label an infant seems clinically impractical. When I write my daily notes and try to provide a diagnosis, I struggle every day to describe what I see. What do we call the condition that preterm infants have when they get over their surfactant deficiency and still need oxygen and respiratory support? My favorite term I used training in Toronto, Canada was “evolving” chronic lung disease. What terms have you used to define this? In every other neonatal condition we call the disease process when it occurs.
So, what would be better than CLD?
We need a term that might capture the essence of the pathophysiology that occurs in this immature stage of lung adaptation. What about the term “pneumonitis of prematurity” or POP, since invariably no matter the reasons the presence of inflammatory changes are present early on.
Mild POP would occur in infants after RDS and then would simply fizzle out (pardon the pun) by the time they reach 36 weeks, while those with more protracted symptoms with inflammation, scarring, and altered state of development would be classified as having moderate to severe POP. Having a term from the start would call the problem what it is, and give it life to manage accordingly. Moreover, it would help parents understand what their child is struggling with.
CLD rates continue
One of the great disappointments over the past decade has been the relative resistance for CLD rates to fall. Each year about 10,000 infants suffer from this condition and often require multiple hospitalization and medical visits after they leave the NICU.
The NICHD data summary for the period 1993 to 2012 showed some great improvement in overall survival for all gestational ages.1 There has been steady reduction in morbidity across most morbidities except for CLD, which was shown to increase over this period. Some, but not all, of this effect was due to improved survival of our smallest preemies.
What causes CLD? So far, our best understanding seems to be a combination of genetic and environmental factors that trigger an acute then chronic inflammatory reaction in the lungs. The changes and damage done to the lungs is a product of underlying remodeling triggered from this inflammation.
What caused the inflammation is multifactorial, due in part to the abnormality of being outside of the womb too early, exposure to oxidative stress, positive pressure ventilation with more volutrauma than barotrauma, and the incitement of inflammatory factors in the lung through antenatal factors or possible infection.
CLD nutrition factors
Some recent data makes me very curious about the prospect that there may be a nutritional solution to CLD.
In a number of retrospective studies, the intake of human milk or an all human milk diet over formula had a significant impact.1-3 What is in human milk that can possibly pass on protection against CLD? Is it based on reduction of inflammation? Or immune modulation? Does it affect vascular growth, as human milk intake also appears to reduce the incidence of the vascular and inflammatory disease of the eye, retinopathy of prematurity (ROP)? Or could it be more that exposure to intact bovine protein may encourage inflammation or alter immune status?
More neonatal misnomers… with a connection
I want to highlight other misnomers in neonatology. For instance, take spontaneous intestinal perforation, or SIP. The truth is, no intestinal perforation I have seen simply occurred spontaneously without provocation. Usually the child is tiny and at risk for lots of things, including dysmotility, and prone to bowel distension and ischemia, etc. The prior name used, focal intestinal perforation, may have been more accurate. At least it says what it is and not how it got there.
There is the acronym ROP for retinopathy of prematurity. We now know that the pathophysiology of ROP lies with vasoproliferation and inflammation. Maybe we should rename it retinovasoproliferation (not a real word I think) of prematurity to keep to the three-letter acronym. Interestingly, there is strong literature that suggests that biologic factors such as IGF1 are low in preterm infants and that this is the major precursor event to ROP. Low IGF1 levels have also been associated with CLD. This raises the possibility of creating a higher order affliction that could be subject to the acronym COP for cytokinemia of prematurity.
And then there are some conditions that don’t have any acronym. Virtually every preterm infant is jaundiced. Usually this is physiologic and representative of immaturity, but some levels of serum bilirubin are too high to just watch. These infants need intense phototherapy but the jaundice and high biilirubing levels generally resolve. But why didn’t we ever call this hyperbilirubinemia of prematurity, or HOP?
We have created pseudo-acronyms like NEC (perhaps we could rename it Necrotizing Enterocolitis of Childhood). NEC is also a scary term for parents. Unfortunately, the disease is scary too. Infants die far too often from this. The statistics remain sobering: We still see 4-7% of VLBW infants getting NEC. About a third of them get surgical NEC and then about half of those that get surgery die! So maybe the name suits it. We have recently begun to understand a key role the gut microbiome has in the pathogenesis of NEC. It seems many intestinal disorders are associated with abnormal microbiome or dysbiosis.
Dysbiosis and Cytokinemia
In medicine we tend to divide into lumpers versus splitters when we look to classify things. Albert Einstein spent his last days trying to bring all the universal forces together into an unifying theory. Is our task then to seek commonalities in preterm disease that actually drive many of our current acronymed diseases?
It is very likely we will recognize that a significant number of preterm infant conditions are actually due to upstream dysbiosis or cytokinemia. Data is emerging that suggests that dysbiosis might play a role in the lung microbiome in CLD. This may only force the creation of more acronyms such as dysbiosis of prematurity or DOP. Something like DOP may in fact rule over all other processes and help us target master processes to improve morbidity outcomes.
The big question I leave you with then is if we fix the DOP with POOP (aka fecal transplants), can we eliminate our NEC, SIP, and CLD in one fell swoop?
- Stoll BJ, Hansen NI, Bell EF, Walsh MC, Carlo WA, Shankaran S, Laptook AR, Sánchez PJ, Van Meurs KP, Wyckoff M, Das A, Hale EC, Ball MB, Newman NS, Schibler K, Poindexter BB, Kennedy KA, Cotten CM, Watterberg KL, D’Angio CT, DeMauro SB, Truog WE, Devaskar U, Higgins RD; Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Trends in Care Practices, Morbidity, and Mortality of Extremely Preterm Neonates, 1993-2012. JAMA. 2015 Sep 8;314(10):1039-51. doi: 10.1001/jama.2015.10244. PubMed PMID: 26348753; PubMed Central PMCID: PMC4787615.
- Patel AL, Johnson TJ, Robin B, Bigger HR, Buchanan A, Christian E, Nandhan V, Shroff A, Schoeny M, Engstrom JL, Meier PP. Influence of own mother’s milk on bronchopulmonary dysplasia and costs. Arch Dis Child Fetal Neonatal Ed. 2017 May;102(3):F256-F261. doi: 10.1136/archdischild-2016-310898. Epub 2016 Nov 2. PubMed PMID: 27806990; PubMed Central PMCID: PMC5586102. PubMed PMID: 27487230.
- Hair AB, Peluso AM, Hawthorne KM, Perez J, Smith DP, Khan JY, O’Donnell A, Powers RJ, Lee ML, Abrams SA. Beyond Necrotizing Enterocolitis Prevention: Improving Outcomes with an Exclusive Human Milk-Based Diet. Breastfeed Med. 2016 Mar;11(2):70-4. doi: 10.1089/bfm.2015.0134. Epub 2016 Jan 20. PubMed PMID: 26789484; PubMed Central PMCID: PMC4782036.
- Spiegler J, Preuß M, Gebauer C, Bendiks M, Herting E, Göpel W; German Neonatal Network (GNN); German Neonatal Network GNN. Does Breastmilk Influence the Development of Bronchopulmonary Dysplasia? J Pediatr. 2016 Feb;169:76-80.e4. doi: 10.1016/j.jpeds.2015.10.080. Epub 2015 Nov 25. PubMed PMID: 26621048.