Tuesday, July 29, 2008

Researchers Link Premature Birth To Emphysema

While this study only included a very small sample (21), I feel it is worth mentioning.


"A small study of 21 infants born up to four months prematurely in the 1980s and weighing as little as 0.6 kilograms showed that by the time they were young adults all had lung problems, including 84 percent who showed areas of emphysema."

"The young adults in the study were born between 1980 and 1987 and were dependent on supplementary oxygen for more than 28 days during their stay in the hospital."


Kristie McNealy said...

Yikes. Perhaps that's another part of the problem with ventilators in the pre surfactant era, or ventilators on immature lung tissue period? Haven't gone to read the article yet, but that is one thing that comes to mind immediately.

Kate K. said...

It wouldn't surprise me if prematurity was associated with future lung problems, such as emphysema.

However, this study has a sample of a mere 21 people in it. It surprises me that one could get published with such a small sample size, especially considering the topic. A lot of Type I Errors (that is, mistakenly finding an association in your sample that doesn't actually occur in the population because of chance, or an odd duck sample) can be made with a sample size of 21.

Given that SES is associated with prematurity and SES is associated with smoking, a convincing study would have to have matched controls. As near as I can tell, there were none.

Again, I wouldn't be surprised if the research hypothesis ends up not being rejected in future studies, but this study just doesn't seem particularly robust.

Sis Sarah said...

I actually know of a couple kids, preemie's that have emphysema now and they are not even 12. looking towards a lung transplant.

Lungs do not do well when they have been damaged. Once they are scarred, they are scarred.

ThePreemie Experiment said...

I agree that it is a small sample size and other factors are not listed. But, being that I know a few adult preemies that have emphysema, I felt it was worth mentioning.

ThePreemie Experiment said...

Krisitie, I wonder if surfactant will prove to hold off long term lung issues. I'm surprised when I see little ones with lung issues that are the same as the ones during the pre-surfactant era.

Kyrsten said...

Does anyone know what happened to the amazing creation one doctor was trying to get approved by the FDA?

I remember reading -ironically, just as Joshua was coming home, so say about a year and a half ago?- about a surfactant that's actually a gel: it coats the lungs of very premature infants and somehow protects them from a lot of the injury commonly associated with immature lungs...

Sorry, I don't have time right now to do more research; 'just wondering if anything's come of this!

Anonymous said...

from Laura

I'm not sure I'm impressed with such a small study. But, vents and little lungs are certainly going to be associated with huge issues.

Our Katie was in one of the first groups to get surfactant. She's ten. As a toddler they used the diagnosis of COPD. I've not heard that for years. I wonder, though, if poorly controlled chronic asthma could have something to do with this association between preemies and emphysema. Thankfully, today we have the benefit of inhaled steroids.

We certainly still deal with pulmonary issues. We have oxygen in the house but use it only every few months. Katie's lungs certainly are not normal. But all things considered she's darn good. I think that most of her pulmonary symptoms are associated with her hypoventilation and not prematurity.

Kate K. said...

Sis Sarah & Stacy:
How long were the preemies that you know who now have emphysema on the ventilator?

I seem to recall one of the neonatalogists mentioning that ventilators had changed in recent years. They are making the "gentler" than they were. Hopefully, that will minimize scarring. On a related note, does anyone know how long CPAPs have been used?

Laura raises an interesting point when she mentions "poorly controlled chronic asthma could have something to do with this association between preemies and emphysema."

Sheila Brown said...

Laura wrote:
Our Katie was in one of the first groups to get surfactant. She's ten

Hi Laura,

Surfactant was
"officially" approved by the FDA after an *extremely* long (by most drug standards) clinical trial period around 1989. The earliest surfactant recipients(from the trial period) are in their 20's now, and the first batch of kids who received it after it became an approved therapy are at least 18.
When my Katie was in the NICU, surfactant was given to any baby in respiratory distress that weighed less than 1500 grams. Even though the drug had full approval, the Neo's at her NICU felt that since RDS in infants over 1500 grams (even in 1990) was *usually* survivable, it didn't warrant the use of a 'new' drug. The common use of that drug corresponds with the tsunami levels of 'survivors' (coupled with explosion of ART in that same time). I hope given the enormous number of available subjects, that other researchers will attempt to confirm these findings since they have an ocean of data available to them.


Kristie McNealy said...


I know what you mean about the surfactant kids. In theory it could actually make some of the numbers worse, because some kids are alive now that wouldn't have made it pre-surfactant. It's obviously a very complicated issue, but I'd love to see a bigger trial and some more recent data.

Our own daughter has chronic respiratory issues, and she got 2 doses of surfactant. The fact that she needed 2 doses, and they heavily debated an unproven 3rd dose, even at an otherwise very robust 31 weeks and 1780g points towards the possibility of other problems (which were later confirmed).

Anonymous said...

Helen Harrison here:

There are a number of other studies on preemies showing more or less the same thing as the study cited here -- lots of adult lung problems of varying degree. So I wouldn't worry about this being "one study" or "a small sample."

Surfactant has done nothing to prevent lung damage. In fact, BPD rates have risen dramatically with the use of surfactant and steroids. There is also evidence that steroids in infancy lead to abnormally poor lung growth later on. I also remember seeing a study recently showing that preemies, even those who were never on vents, are still vulnerable to long term lung problems.

I'm just back from a trip, but as soon as I'm unpacked and settled back in, I'll try to get the references for the
late-childhood-adult-preemie lung follow-up studies.


Anonymous said...

Here are the questions that I have:
Were the researchers only looking at one variable--surfactant vs. no surfactant? Was the study controlled for all other variables
--for example, the use of steroids (to wean kids off their vents)? As Helen notes, the use of steroids could confound the conclusions--in plain language, did the damage result from surfctant use/no surfactant? From time on the vent? From the use of steroids to get the kiddo off the vent? Or from pneumonia? Or some other reason?

Emphysema is a disease characterized by over-inflation of the air sacs such that their walls rupture and there are large areas of consolidation/coalescence, that is, large air pockets where we would rather see discreet individual tiny air sacs. The many membranes that are destroyed (by mucous)are necessary, as gases are exchanged across the membranes, and you need a large surface area/intact membtranes in order to have good gas exchange. Emphysema IS a chronic obstructive pulmonary disease (COPD).

The surfactants have evolved since 1989. They have improved. The first surfactants were porcine.
Surfactant is alread thick and viscous--a lot like the look of Mylanta, thick and chalky. The child receiving surfactant is turned from side to side during the administration and for a time thereafter, so that the viscous liquid can coat all the structures.

Another change that I am aware of is that at the current time, there is a time-frame for giving surfactant--within 25 min. of delivery is my hospital's standard, I believe. The elapsed time since delivery (in the past) could be a variable that you would need to control for, as well as all the other variables.

Chris and Vic

Anonymous said...

From Helen Harrison to Chris and/or any other medical professional, or informed non-professional, who would care to comment:

We have just been through another nightmare with Ed in late June (see previous posts in previous threads) in which Ed experienced a lung shut-down, diagnosed as pneumonia, which, this time, also led to a heart attack.

This is Ed's third episode of "pneumonia" -- since 2004.

What I'm wondering is this: can emphysema be diagnosed even when it co-exists with pneumonia?

The current hypothesis about Ed's inability to breathe properly (and his constant tachypnea and tachycardia)is that his abdomen is so distended from adhesions (from prematurity-related shunt surgery) that he can't breathe properly. Ed's abdomen is quite distended and his doc says it is not fat.

The CT scans do not show any obvious obstruction or fluid build-up.

I'm wondering if what Ed is going through is simply the (reported) 100% rate of prematurity-related lung malfunction later in life.

Ed is 32 years old.


mom to lilike locke anjeni said...

My daughter Lilike had TTN. TTN is also called "wet lungs" or type II respiratory distress syndrome. ... with TTN, the release of the hormone epinephrine is inhibited during labor.

Symptoms of TTN include:

rapid, labored breathing (tachypnea) of more than 60 breaths a minute
grunting or moaning sounds when the baby exhales
flaring nostrils or head bobbing
retractions (when the skin pulls in between the ribs or under the ribcage during rapid or labored breathing)
cyanosis (when the skin turns a bluish color) around the mouth and nose
Other than the above symptoms, infants who have TTN will look fairly healthy.

Newborns at higher risk for TTN include those who are:

delivered by cesarean section
born to mothers who smoked during pregnancy
born to mothers with diabetes
small for gestational age (small at birth)
rapid nvd
(Lilike was born via rapid nvd)

mom to lilike locke anjeni said...

After babies with TTN receive special monitoring and treatment in the hospital, they usually recover fully. Some studies, though, suggest that they might be more likely to develop wheezing later in life.

RhondaLue said...

Hey Stacy....would you mind emailing me privately? I have a couple of questions about Paige and her history that I'd like to pick your brain about.

No hurry, I know you just got back home.

ThePreemie Experiment said...


I think you may not be getting my emails. I responded when you sent a note the on line support group we are both on. I'll try again right now from my private email but if you don't get anything please email me through my blog thepreemieexperiment@gmail.com with your phone number and I'll call you.


Anonymous said...

From Helen Harrison:

While we are on the topic of the consequences of ventilator/oxygen therapy, I thought I'd share a reference recently sent to me by Dr. Doug, the neonatologist that some of you may remember from preemie-list and preemie-child. This study may hold clues as to why brain bleeds and PVL aren't the whole story on preemie outcomes.
Myelin Expression Is Altered in the Brains of Neonatal Rats Reared in a Fluctuating Oxygen Atmosphere

Kofi Sedowofia, David Giles, Jean Wade, Steve Cunningham, Janet R. McColm, Robert Minns, Neil McIntosh

Child Life and Health Section, Division of Reproductive and Developmental Sciences, University of Edinburgh, Edinburgh, UK
Address of Corresponding Author

Neonatology 2008;94:113-122 (DOI: 10.1159/000119721)


Anonymous said...

From Helen Harrison:

I promised earlier to come back with some more studies on longterm lung damage in preemies.

Here are a few studies I have right at hand...I'll keep updating the list as I find them.

The first is from the Society for Pediatric Research (SPR) meeting that I attended in May.

The study is from the EPICure group in the UK which studies long term outcomes in under 26 weekers.

At age 11, 219 extremely premature (EP; <26 week g.a.) children were given lung function tests before and after being given salbutamol (a bronchodilator). Their lung function was compared with a control group of term-born children of the same age.

Conclusions: At 11 years of age, EP children have highly significant impairments in lung function measures and responses to bronchodilators. These changes may have important consequences for adult health. [Fawke et al. The EPICure Study:Respiratory Outcomes at 11 years. SPR abstracts are available in their entirety at the SPR website]
The next study looks at bigger preemies and is in the American Journal of Respiratory and Critical Care Medicine. 2007;176:1269-1273.

It only examines the first two years of life but finds no period of catch-up during this time in lung function for preemies compared to full-term infants, even in preemies who were born relatively big and healthy (the mean gestational age in the study was about 33 weeks). The authors suggested future studies to determine why preterm infants have persistent deficits in lung function, such as possibly increased bronchial tone, more compliant airways, and/or decreased pulmonary elastic recoil.
A study looking not at formal lung function but just at respiratory diagnoses in ELBW(<1000 grams) children at ages 8-12 found that, overall, 78% had chronic health problems that included ADDH, autism, OCD, and anxiety disorder as well as the usual "severe" disabilities (CP, retardation, hearing loss, blindness, etc.). Thirty-two per cent of the children had "breathing problems" and 27% had "allergies." Forty-two per cent had more than one condition, and 36% had limited functioning at school because of physical problems.

Slightly off topic here, but very important I think, was a study presented at SPR by Davis et al. from University of California, Irvine. It was entitled "Prenatal Exposure to Glucocorticoids Affects Growth in Full Term Infants." The study demonstrated that only *one* dose of betamethasone adversely affected size, weight and head circumference (i.e. brain growth) in full-term infants!

The authors state: "The effects of prenatal glucocorticoid treatment on fetal growth are of particular concern because accumulating evudence indicates that small size at birth, even within the normal range, has lasting implications for adult health."

Previous animal studies have shown that early steroid exposure distorts and reduces lung growth and development.

I also have to wonder how many fullterm children diagnosed with autism were exposed to prenatal steroids.