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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Refractory asthma: Bronchoscopy may guide effective therapy (CHEST)