I have a 14 year-old female with very severe asthma. She has had many tests and meds do not help. She is currently on prednisone 20mg BID and still wheezing.
Sweat test ne.
Ig levels normal.
Cilia biopsy normal.
Allergy testing: IgE 600, +aspergillus igE. IgG aspergillus neg.
She had peripheral eosinophilia, hx bronchiectasis on imaging.
Treated for ABPA with oral steroids and intraconazole for 2 months.
Xolair did not help.
Bronchoscopies: increased PMN, and eos. mild elevated pepsin. cultures neg.
ph probe + on gerd therapy.
ANCA and ANA and complement negative

She is currently on Xolair, Singulair, Symbicort 160, Zyrtec, Spiriva, Pulmozyme, Prednisone 20mg BID.
Plaquenil 200mg BID (for asthma)
She was hospitalized 2 wks ago and last week for asthma.

The current plan is to get approval for bronchial thermoplasty (not approved due to age). Any further treatment or diagnostic tests?


Thank you for your inquiry.

First, let me say that I think you have done due diligence with a superb workup and therapy. I do not think there is any stone you have left unturned, and at this particular point, the only other therapies that one might consider would all be “off label,” and I would not pursue them until which time you have tried bronchial thermoplasty, as you have scheduled.

As far as alternative therapies to be considered in the future, these would of course require special approval. Things such as anti-IL5, anti-IL13, anti-IL6, TNF therapies, et cetera, could be considered in the future if she failed to respond.

Lastly, adherence is always a difficult issue to assess. I am sure that you have done so, but you might consider a test of adherence by measuring her peripheral eosinophil count and then giving her a high dose course of prednisone over 7 days (60 to 40 mg a day), and repeating the eosinophil count at the end of that period. Even in a severe asthmatic such as your patient, the eosinophil count should fall on this dose over that length of time. If it does not, it might give a clue as to lack of adherence to therapy. The same thing could be accomplished using theophylline and checking a serum level.

Finally, we have several postings on recalcitrant asthma you might find helpful. You can access them by entering "recalcitrant asthma" into the search box on our Ask the Expert website. For your convenience one of these is copied below:

I have a patient with steroid dependent asthma (the only patient I have who suffers with this as he has failed all other treatments) determined by his pulmonologist who has been treating him with widely variable doses (10-60 mg) of Prednisone constantly for the last 15-20 years. Of note, this pulmonologist is and excellent physician who has tried EVERYHING in this patient, including Xolair, to which he anaphylaxed. The patient is very compliant with his treatment and also has excellent inhaler technique.

This poor man also suffers with nasal polyposis, for which he has had several surgeries, and recurrent sinusitis that generally occurs only when his prednisone dose is decreased so that his polyps flair. He has had one pneumonia that was successfully treated as an outpatient many years ago, and which was not related to the one ICU admission (and this was his only hospitalization) requiring intubation for a full week.

I had ordered serum immunoglobulins, subclasses,pneumococcal, and tetanus titers back in March 2011 and noted that His total serum IgG was low 550 (694-1618 mg/dL)along with decreased subclasses 1, 2, and 3, and pneumococcal titers that were all < 0.3. He received a Pneumovax (which he had never had before) and then failed to follow up for > 1 1/2 years (personal reasons). During that time he had a couple of episodes of sinusitis which resolved with oral antibiotics and increased doses of Prednisone. I have recently repeated his pneumococcal titers, and even at this late date, he has protective titers to 9 of 14 serotypes. I have referred him to ENT for another evaluation of his polyposis, and perhaps another procedure if it is felt to be appropriate. His tetanus titers are great at > 7.00 (>0.15IU/mL). His repeat serum IgG is still low at 566(same normal range) with subclasses 1-3 being low as well.

I believe that it probably would have been best if I had not done any of this testing in the first place as he has been on oral steroids for so many years, and often at doses exceeding 30 mg/day. Other than recurrent sinusitis, which improves quickly with antibiotics and increased doses of steroids, he has not suffered with infections. Unfortunately, I am left with the results with which I think that nothing should be done.

By the way, a sweat test was also negative.

Your opinion please?

Thank you for your inquiry.

I am not certain from your inquiry whether you are asking a specific question such as whether or not immunoglobulin replacement therapy might be of help to your patient, or whether you are simply asking for general comments. Since you did not cite a specific issue, I have made the following comments very general.

Recalcitrant asthma is a problem that most allergists/immunologists will face periodically and, as you know, there have been numerous publications dealing with this issue. In your particular patient, since you mentioned that the pulmonologist caring for him has tried “everything,” I assume that multiple alternative treatments have been suggested. Nonetheless, not being sure of this, I would like to call your attention to several therapies which, in some instances, have seemed to be helpful in cases such as the one you have described. It is clear, however, that these modalities are not universally effective and, therefore, their use in any individual patient is to be considered a matter of trial and error. However, in your patient, it would appear that any therapy that has shown any usefulness in the past, and has not been tried in your patient, should be considered.

I apologize if these treatments have already been tried, but I do want to mention them nonetheless.

1. Methotrexate
2. Cyclosporin or tacrolimus
3. Gold
4. Hydroxychloroquine
5. High dose immunoglobulin replacement
6. Bronchial thermoplasty
7. Anti-TNF alpha
8. Anti-IL6
9. Anti-IL13
10. Aspirin desensitization if your patient has aspirin sensitivity

As noted, the use of these agents has been limited to recalcitrant cases such as your patient, and they have not been effective in all instances, but there is theoretical evidence for their efficacy and there have been isolated patients who have appeared to respond to each.

Of these, immunoglobulin replacement, since your inquiry seems to imply that you are considering immunoglobulin replacement treatment, might be a reasonable choice for your patient. The doses, however, used for asthma therapy are often somewhat higher than those normally given for primary immunodeficiency disorders.

There are references in the literature that you could obtain for each one of these treatments by searching PubMed or Google by typing in the particular drug and following with the entry of "asthma". Since, however, as mentioned, immunoglobulin replacement treatment seems a reasonable choice, I have copied below an abstract discussing this treatment.

I might also mention, for diagnostic purposes, you should consider Churg-Strauss in this patient. With the high dose of prednisone the patient was taking, one would not expect to see eosinophilia. If an ANCA has not been ordered, I would also consider doing this as well.

Allergy Asthma Proc. 2006 Jan-Feb;27(1):53-8.
The response to intravenous immunoglobulin replacement therapy in patients with asthma with specific antibody deficiency.
Schwartz HJ, Hostoffer RW, McFadden ER Jr, Berger M.
Department of Pediatrics, Rainbow Babies and Children's Hospital and University Hospitals of Cleveland, Cleveland, Ohio 44106, USA.
In a retrospective analysis of our patient population, 20 difficult-to-treat patients with asthma were found to have clinical and laboratory evidence of specific antibody deficiency, and several had mild hypogammaglobulinemia. Intravenous immunoglobulin replacement therapy at 400-600 mg/kg every 3-4 weeks gave remarkable clinical benefits, with reduction in morbidity, number of hospitalizations, steroid therapy, and number of respiratory infections. We believe that, in this group of patients, the use of intravenous immunoglobulin perhaps allows the achievement of asthma prevention rather than an amelioration of inflammation.

Thank you again for your inquiry and we hope this response is helpful to you.

Phil Lieberman, M.D.

Close-up of pine tree branches in Winter Close-up of pine tree branches in Winter