treatments

Question

In which situations can anti-inflammatory drugs (steroidal or non-steroidal) be used to treat cystic fibrosis (CF)?

Answer

Hello,
Your question is a very good one.
In CF there is a vicious cycle ‘inflammation-infection’, especially on the level of the bronchial tree and also on the level of the pulmonary tissue.
The hydro-electrolytic abnormalities caused by the CFTR protein dysfunction create an abnormal viscosity of the respiratory secretions. Nowadays, we know that – already amongst newborns - a state of abnormal inflammation exists. Besides, it is the current understanding that the antibacterial defences are altered at the level of the respiratory secretions and that this promotes bacterial colonisation/infection of these secretions. Indeed, every person with CF presents a bacterial colonisation of the respiratory mucus.

The host – person with CF – will the try and eliminate the bacteria. The activation of his/her immune system leads to an attraction of white blood cells (neutrophils) to the bronchial tree. The neutrophils try to eliminate the bacteria by secreting a number of substances which are toxic for the bacteria, but unfortunately these substances are also toxic for the bronchial and pulmonary tissue. Thus, the inflammatory response is on one hand beneficial (elimination of the bacteria) and on the other hand harmful (damage to the bronchial and pulmonary tissue).
Theoretically at least, the use of anti-inflammatory drugs could be useful in persons with CF if the inflammatory response is too violent.

The prototype of non-steroidal anti-inflammatory drugs is ibuprofen, which is sometimes used in CF, mainly in children and mainly in the US. Of note: even in the US less than 5% of patients take this drug. The reason for that is that - as with a lot of other treatments in CF - there aren't any correctly conducted studies to evaluate the efficacy of this treatment.
The Cochrane Collaboration, named after Archibald Cochrane, a famous epidemiologist from the UK, publishes systematic review evaluating the effect of particular health interventions. The last Cochrane review concerning the benefits of anti-inflammatory drug treatment in CF dates from 2007 and lists six correctly conducted studies. However, these studies examined less than 300 persons in total, and two of these studies included partly the same persons. The medications examined were ibuprofen and piroxicam. The review’s conclusion is that the administration of ibuprofen can reduce the annual decline of lung function in CF, particularly in children and/or persons who have only slight respiratory involvement from CF. No major side effects have been reported. Nonetheless, like I said above, even in the US, this practice isn't very popular and in Europe it is not a major success either. In my opinion this is due to two reasons. First of all the missing proof, second the fear of side effects. High doses of ibuprofen have to be administered and ideally the blood levels of the drug have to be checked and this type of treatment can cause peptic ulcers and/or contribute to kidney failure.

Other categories of anti-inflammatory drugs exist: leukotriene inhibitors or antagonists, statins and other categories of more experimental molecules. There have already been studies conducted in CF, but none has been conclusive yet. Azithromycin is nowadays the most exploited molecule with anti-inflammatory properties.

Concerning corticosteroids, a Cochrane review in 2011 listed 3 studies including ~ 350 participants: two of the studies were conducted over 4 years, the third one during 12 weeks. The conclusion of the review was that administration of 1-2 mg/kg of prednisolone one day out of two can reduce the functional respiratory loss over the long term. However, the administration of corticoids can very significantly slow down growth in children and have other multiple harmful side effects. One of the 4 year studies had to be interrupted because of side effects. Interestingly, at a follow-up10 years after the end of one of these studies, it has been noticed that the children present catch-up growth two years after the end of the intake of steroids. Therefore, the benefit of giving steroids over a longer term has always to be weighed against the risk of important side effects.
We have less information concerning short-term steroid administration. In practice, a short corticotherapy is often prescribed in case of severe pulmonary exacerbations (particularly for the viral bronchiolitides like RSV, adenovirus infection,…) and/or when exacerbations - for unknown reasons - aren't readily responding to the conventional treatment.

Oral corticotherapy is also needed to treat allergic broncho-pulmonary aspergillosis, but this goes past your question.

That's it. I hope my answer will help you,
Sincerely yours,
Christiane Knoop

22.03.2012