Refractory asthma: Bronchoscopy may guide effective therapy (CHEST) - PulmCCM
Mar 242012

(Comments by first author James T. Good follow this post.)

For 58 patients with refractory asthma at National Jewish, James Good et al devised a systematic, bronchoscopy-driven approach that they feel resulted in improved asthma symptoms and identification of potential phenotypes of refractory asthma among the enrolled subjects.

Their methodology was highly detailed and time- and labor-intensive. It included using the supraglottic index (a grading system described in the ENT literature) and eosphageal pH probes to quantify GERD; airway survey to quantify the "bronchitis index"; BAL and/or brushings with PCR and culture to identify subacute bacterial infection; and endobronchial biopsies. After their workup:

  • 22 patients were deemed the "GERD phenotype."
  • 13 patients were the "subacute bacterial infection phenotype."
  • 4 were "tissue eosinophilia phenotype"
  • 13 were a combination.

They then "targeted treatment" for 12-60 weeks with proton pump inhibitors, Nissen fundoplication in 7, Xolair for tissue eosinophilia, and/or antimicrobials according to culture/PCR results. (In addition to high-dose ICS, Singulair, etc.)

They describe remarkable statistically significant improvements after all this in most/all groups: 7 points in the Asthma Control Test and 15% predicted FEV1, overall. Authors did not report other important outcomes data like exacerbations, ED visits or prednisone use.

As there was no control group, it's hard to rule out a placebo or "tincture of time" secular effect, due to the patients' personal investment, and all the personal attention from national experts. It would be hard to implement this widely, but if the findings were replicated and harder outcomes were also shown to be improved, it would be a persuasive argument for funding specialized refractory asthma centers with standardized treatment protocols.

A specific concern with their GERD findings is that in the absence of GERD symptoms like heartburn, treating asymptomatic GERD (identified using pH probes, as was done here) has not been shown to improve asthma in randomized trials.

The NHLBI has an ongoing severe asthma project that seeks to identify phenotypes of refractory asthma and standardize research on human subjects across the U.S.; U. of Colorado is one of the centers.

Good JT et al. Refractory Asthma: Importance of Bronchoscopy to Identify Phenotypes and Direct Therapy. CHEST 2012;141:575-576.

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  3 Responses to “Refractory asthma: Bronchoscopy may guide effective therapy (CHEST)”

  1. At National Jewish Health we see a large number of patients with refractory asthma (Am J Respir Crit care Med. 200;162(6):2341-2351). Standard evaluation includes tests of pulmonary physiology including bronchial provocation, allergy evaluation with skin testing, IgE levels, eosinophil counts, serologic markers for vasculitis, radiographic studies including chest x-ray (or chest CT when indicated), sinus CT and barium swallow as well as esophageal pH-impedance studies. Because asthma is a disorder of the airway we reasoned that careful visual inspection of both the upper (supraglottic) and lower airways, coupled with endobronchial biopsies, bronchoalveolar lavage and brushings could help us better define the major reason(s) for poor asthma control (i.e. asthma phenotype). While there was no control group, the first 20 patients were treated with therapeutic interventions based on data from all the above-mentioned studies without significant improvement in the FEV1 or the asthma control test (ACT). After bronchoscopy, with adjustments in therapy based on the bronchoscopic phenotype, there were significant improvements in both FEV1 and ACT. The next 38 patients with refractory asthma had bronchoscopy in addition to our standard work up and when they could be phenotyped (reflux, tissue eosinophilia, subacute bacterial infection, or combination) there was significant improvement in pulmonary function and ACT. There was no such improvement in the nonspecific group. We realize that this is a small group of patients and other centers need to confirm our findings. It is our bias that in these refractory asthmatics, early bronchoscopy with directed therapy based on these clinical phenotypes will lead to improved asthma control. We are continuing to follow most of these patients and monitor asthma control. In a small number of patients who have had relapses with persistent poor control we have performed repeat bronchoscopy and been able to identify a change in phenotype. It is critical that as physicians treating patients with asthma we remind ourselves there are numerous factors (irritant, immunologic, environmental, and infectious) that may contribute individually or collectively in preventing asthma control. Bronchoscopy appears to be a powerful tool in identifying those factors.

  2. While ACE inhibitors may augment the role of substance P in decreasing reflux, by symptoms, sighns of regurgitation and microaspiration, PH metry and endoscopy may detect GERD and control it. Eosinophilia or certain allergens may persuade physician to use antihistamines and corticosteroids. Also infections has their own manifestations, besides PFT and response to bronchodilators are good tools. If it is new onset asthma and severe exacerbation of it , it needs more diagnostic assessment as CT scan, and brocchoscopy to seek for local tumor with metastasis, aspergilosis,vasculitis, parasitosis, and other diseases. We had a patient with complaint of sinusitis and whiizing and the final DX was lung adenocarcinoma with multiple metastasis to brain. If it is a collagen vascular disease or sarcoidisis suspicious, it is mandatory to perform bronchoscopy and BAL and cytology and biopsy to see the cells and R/O infections before pulse therapy. Otherwise routine bronchoscopy in asthmatic may perpetuate a crisis and hypoxemia. thanks

  3. I have adopted this approach in my practice and have been impressed. First of all, I had to read the paper on the Reflux Finding Score. Immediately I began to see findings of reflux that I had seen numerous times before, but had been unable to interpret because I, as a pulmonologist, was never taught anything about laryngeal physical exam. From there I intervened in ways that I had not previously, such as ENT consultation, and have had patients do better. I’ve also found multiple cases of subacute bacterial infection. As far as I can tell, this is not a well understood entity, but in many of my refractory asthmatics it seems to be present, and treating it helps. I’ve not found persistent tissue eosinophila despite diligently looking for it. I think that this paper throws light on a variety of other papers in asthma. First of all, sometimes azithromycin and Nissen fundoplication helps, but not in everyone. Asthma is refractory to standard treatment for different reasons in different people. But there aren’t that many different reasons. This paper does for asthma what Irwin has done for chronic cough. 90% of refractory asthma is laryngopharyngeal reflux, subacute bacterial infection, or persistent tissue eosinophila. Figure out which are playing a role, and deal with them, and your patients will do better. Works for me.