Pulmonal damage

Question

Hello,
In case a child with CF can nearly never expectorate sputum after inhalation of 6% hypertonic saline, and also otherwise there are no problems with cough or the airways, can one then assume, that the lung is not as strongly involved by the CF?
Is it true that there are in general two different forms of manifestation:
on the one hand patients who show more a pulmonary involvement, but rather have few gastro-intestinal problems, and on the other hand those, who have a gastro-intestinal manifestation and few pulmonal problems?
How is the damage of the lung exactly happening if there is no obvious mucus production in the lung, no "problematic germs" have been found and no (obvious) infections did occur?
Can a consequent inhalation scheme (6% hypertonic saline and rh-DNAse) prohibit these lung damages or at least slow them down, if a patient inhales from birth on regularly?
Many thanks for your time and advice!

Answer

Hello,
The questions asked by you are very intelligent and are a great challenge for the expert. The question can however be answered clearly:
The inflammation of the bronchial system is already starting in the first few weeks of life! Depending on the changes of the acid milieu of the mucosa, bacteria can grow more or less and then cause an inflammation and infection with all its consequences. If now after the inhalation with 6% hypertonic saline or/and rh-DNAse few mucus is getting lose, this does not mean that there is no inflamation or infection at all and that there is no mucus present.
If we want to know the exact state of inflammmation, we would have to do already at newborn age respectively in the first weeks of life the following invasive investigations:
- bronchoscopy
- MRI image of the lungs
- measurement of the lung-clearance index (judgement of the inflammation state)
- serological measurement of certain interleukines (markers of inflammaton)
- measurement of the ph-milieu of the bronchial mucosa: reduced pH in the ASL (fluid on the mucosa) is inhibiting anti-microbial activities, therefore increasing acidity (acid content) impairs the killing of bacteria (experiement with CF-pigs)

In general, we are content with the thoughtful treatment and among this the early ant-inflammatory inhalation therapy (6% NaCL and also probably the inhalation with rh-DNAse). Even if only few mucus can be coughed up from the lungs, there are in general still increased amounts of secretions present, that can also be mobilized well via the airway therapy. Therfore the early airway therapy by special trained physiotherapists is already in the first months of life part of the standard therapy!

Your question:
In case a child with CF can nearly never expectorate sputum after inhalation of 6% hypertonic saline, and also otherwise there are no problems with cough or the airways, can one then assume, that the lung is not as strongly involved by the CF? [end of the question]

I would clearly say yes! When exactly the lung is increasingly involved in infections and inflammatory reactions, one can not exactly make this out. Prevention is always better that just "running behind" and trying to treat the damage that already occured. Indeed there are very many factors, that influence the structural changes of the lungs. A great influence have in any case bacteria, that are quite easy to get via microbiological measures with the help of a deep throat swab. This stays in the experience and skills of the CF physician, to react adequatly on the bacterial findings.

Your question:
Is it true that there are in general two different forms of manifestation:
on the one hand patients who show more a pulmonary involvement, but rather have few gastro-intestinal problems, and on the other hand those, who have a gastro-intestinal manifestation and few pulmonal problems? [end of the question]

Indeed there are some CF patients, who are "pancreatic sufficient". In those patients, we find only few gastro-intestinal problems. This group is striking with pulmonal symptoms.
There are on the other hand patients, who show only few pulmonal symptoms but suffer from gastro-intestinal symptoms.

Your question:
How is the damage of the lung exactly happening if there is no obvious mucus production in the lung, no "problematic germs" have been found and no (obvious) infections did occur? [end of the question]

- CFTR is produced/not correctly produced ealry in the development. So, changes in utero would be plausible. However, only short after birth, the sturctural abnormalities of the trachea occur, included the narrowing of the proximal airways (cartilage, changes of the submucosal glands and prominent muscular strains of the smooth muscle) in case of CF-piglets, - mice and - rats.
- CFTR = protein = chloride channel

The hyperplasia of the goblet cells of the mucosa and the changes of the function of the chloride channel are in the end responsible for the lung damage that occur instantly in the course of life. Frequently, the CFTR function is still relatively sufficient. Then the structural changes of the lung are developing more slowly.

Your question:
Can a consequent inhalation scheme (6% hypertonic saline and rh-DNAse) prohibit these lung damages or at least slow them down, if a patient inhales from birth on regularly? [end of the question]

Consequent inhalation of e.g. rh-DNAse daily and 6% NaCL in case of bronchopulmonal infections additionally can for sure slow down the damage of the lungs. The hypertonic saline sloultion has to be tolerated well. Physiotherapy is essential. Personally, I would prefer the inhalation of rh-DNase as a permanent inhalation without additional bronchial reactions.
The early intervention, that is especially possible in countries where a newborn screening is done, show a marked benefit, a better surival curve and markedly lower infections with Pseudomonas of the lungs, also the BMI (bodymass index) is increased and also the lung function (FEV1).
Therefore I would answer your question with a clear "yes"!
Further requests are possible, especially at your CF-center.

Best regards,
Dr. H.-E. Heuer

06.05.2016