Asthmatic granulomatosis: a novel disease with asthmatic and granulomatous features

Am J Respir Crit Care Med. 2012 Sep 15;186(6):501-7. doi: 10.1164/rccm.201203-0476OC. Epub 2012 Jul 5.


Rationale: Severe asthma represents 5-10% of all asthma, yet remains problematic and poorly understood. Although it is increasingly recognized as consisting of numerous heterogenous phenotypes, their immunopathology, particularly in the distal airways and interstitium, remains poorly described.

Objectives: To identify the pathobiology of atypical difficult asthma.

Methods: We report 10 from a total of 19 patients (17 women and 2 men) meeting asthma and severe asthma definitions, requiring daily systemic corticosteroid (CS) use, with inconsistent abnormalities on chest computed tomography scans, who underwent video-assisted thoracoscopic biopsies for further diagnosis and management.

Measurements and main results: The pathology of 10 of the 19 cases revealed small airway changes consistent with asthma (eosinophilia, goblet cell hyperplasia), but with the unexpected finding of interstitial nonnecrotizing granulomas. These patients had no evidence for hypersensitivity pneumonitis, but 70% of cases had a personal or family history of autoimmune-like disease. The 10 cases were treated with azathioprine, mycophenolic acid, methotrexate, or infliximab. Nine of 10 showed decreased CS requirements and improved or maintained FEV(1) despite lower CS doses. Of the remaining nine patients, six manifested asthmatic small airway disease, alone or in combination with alveolar septal mononuclear cells, but no granulomas, whereas three manifested other pathologic findings (aspiration, pneumonia, or thromboemboli).

Conclusions: These data suggest that a subset of severe "asthma" manifests a granulomatous pathology, which we term "asthmatic granulomatosis." Although identification of this disease currently requires a thorascopic biopsy, alternative approaches to therapy lead to improvement in outcomes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenal Cortex Hormones / therapeutic use
  • Adult
  • Aged
  • Airway Obstruction / etiology
  • Airway Obstruction / pathology
  • Asthma / complications*
  • Asthma / drug therapy
  • Asthma / pathology*
  • Biopsy, Needle / methods
  • Bronchodilator Agents / therapeutic use
  • Case-Control Studies
  • Disease Progression
  • Female
  • Follow-Up Studies
  • Granuloma, Respiratory Tract / complications*
  • Granuloma, Respiratory Tract / drug therapy
  • Granuloma, Respiratory Tract / pathology*
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Respiratory Function Tests
  • Retrospective Studies
  • Risk Assessment
  • Severity of Illness Index
  • Survival Rate
  • Thoracic Surgery, Video-Assisted / methods
  • Thoracoscopy
  • Time Factors
  • Tomography, X-Ray Computed / methods
  • Treatment Outcome


  • Adrenal Cortex Hormones
  • Bronchodilator Agents