Scientists “Speak” on Mold Allergy

Background

  • Allergic bronchopulmonary aspergillosis is a pulmonary disorder caused by hypersensitivity to Aspergillus fumigatus, and rarely other Aspergillus species, and is characterized by chronic asthma, recurrent pulmonary infiltrates, and bronchiectasis.
  • An ABPA-like syndrome called allergic bronchopulmonary mycosis is indistinguishable from ABPA but is caused by other fungi.
  • The condition occurs almost exclusively in patients with cystic fibrosis (CF) or asthma.
  • The global prevalence of allergic bronchopulmonary aspergillosis is reported to be 2.5% (range 0.7%-3.5%) among adults with asthma and reported to be 2%-15% in patients with cystic fibrosis.

Evaluation

  • Suspect allergic bronchopulmonary aspergillosis (ABPA) in patients with asthma or cystic fibrosis who have symptoms consistent with ABPA, such as:
    • difficult-to-control asthma
    • new or worsening cough
    • dyspnea
    • increased sputum production
    • expectoration of brown-black mucus plugs
    • wheezing
    • hemoptysis
  • ABPA may also be suspected in patients with computed tomography (CT) findings of bronchiectasis, especially central bronchiectasis.
  • Multiple sets of diagnostic criteria exist, all of which include a combination of clinical signs, imaging findings, and serologic features.
    • Rosenberg-Patterson diagnostic criteria for patients without cystic fibrosis (most commonly used):
      • major criteria for diagnosis (at least 6 required for diagnosis):
        • asthma
        • transient pulmonary opacities on imaging (fleeting shadows)
        • positive skin test for Aspergillus (type 1 immediate hypersensitivity)
        • peripheral blood eosinophilia (> 1,000 cells/mcL)
        • precipitating antibodies (immunoglobulin [Ig] G) against Aspergillus fumigatus in serum
        • elevated total IgE > 1,000 units/mL
        • central/peripheral bronchiectasis with normal tapering of distal bronchi
        • elevated A. fumigatus-specific IgG and IgE
      • minor criteria:
        • Aspergillus in sputum
        • brownish black mucus plugs in expectorate
        • delayed type III skin reaction to Aspergillus
    • Cystic Fibrosis Foundation diagnostic criteria for patients with cystic fibrosis:
      • classic case (all criteria required):
        • acute or subacute clinical deterioration (cough, wheeze, exercise intolerance, increased sputum, decrease in pulmonary function, exercise-induced asthma) not attributable to other cause
        • serum total IgE > 1,000 units/mL (2,400 ng/mL) in patient not on corticosteroids
        • immediate skin reaction to Aspergillus (wheal > 3 mm diameter with erythema in patient not on antihistamines) or positive serum IgE antibody to A. fumigatus
        • precipitating antibodies to A. fumigatus or serum IgG antibody to A. fumigatus
        • recent or new infiltrates or mucus plugging on chest x-ray or bronchiectasis on chest computed tomography (CT) that does not clear with antibiotics or chest physiotherapy
      • minimal diagnostic criteria:
        • acute or subacute clinical deterioration not attributable to other cause
        • serum total IgE > 500 units/mL (1,200 ng/mL) (if disease suspected and serum total IgE is 200-500 units/mL, repeat testing in 1-3 months)
        • immediate skin reaction to Aspergillus or positive serum IgE antibody to A. fumigatus
        • 1 of following:
          • precipitins to A. fumigatus or IgE antibody to A. fumigatus
          • recent or new infiltrates or mucus plugging on chest x-ray or bronchiectasis on chest CT that does not clear with antibiotics and standard chest physiotherapy
      • diagnosis of ABPA in cystic fibrosis should not be based in serology and skin tests only(2)

Management

  • Treatment goals include:
    • control of symptoms of asthma and cystic fibrosis
    • prevention or treatment of pulmonary exacerbations of allergic bronchopulmonary aspergillosis (ABPA)
    • reducing or remitting pulmonary inflammation
    • avoiding progression to end-stage fibrotic or cavitary disease
  • No large randomized trials have evaluated efficacy of various treatment options as of September 20, 2017.
  • Refer patients with suspected or known ABPA to a pulmonologist or an allergist-immunologist.
  • Systemic corticosteroids are considered the cornerstone of therapy for ABPA.
    • In patients with asthma:
      • typical initial therapy is prednisone 0.5 mg/kg/day (or equivalent) with tapering dose as symptoms improve
      • for patients with mild exacerbation – inhaled corticosteroids and bronchodilators may help control symptoms
      • for patients with acute exacerbation – prednisone 0.5-1 mg/kg/day for 1-2 weeks, then 0.5 mg/kg every other day for 6-12 weeks following remission, then tapering dose to preexacerbation dose
      • for patients with refractory disease with multiple asthmatic exacerbations – chronic corticosteroid therapy suggested, usually > 7.5 mg/day
      • dosing may be increased based on findings from routine monitoring of serum immunoglobulin E (IgE) levels, pulmonary function tests, and chest imaging, such as:
        • significant increase of IgE levels (such as doubling of baseline IgE level)
        • imaging evidence of infiltrates, mucoid impaction, fibrosis, worsening bronchiectasis, or worsening physiology
    • In patients with cystic fibrosis:
      • oral corticosteroids indicated for all patients except those with corticosteroid toxicity
      • typical initial dose prednisone (or equivalent) is 0.5-2 mg/kg/day orally to maximum 60 mg/day for 1-2 weeks, tapering to 0.5-2 mg/day every other day for 1-2 weeks with attempt to taper completely within 2-3 months
      • in patients with relapse, increase corticosteroid dose, add itraconazole, and taper corticosteroids when clinical status improves
  • Inhaled corticosteroids and methylprednisolone IV pulses may be used in some situations.
  • Consider antifungal agents in adults with severe, poorly controlled asthma and ABPA (Weak recommendation).
  • Combination antifungal/corticosteroid (nebulized amphotericin B and nebulized budesonide) may reduce the incidence of exacerbations.
  • Omalizumab may reduce exacerbations but may not improve or affect lung function or quality of life.
  • For refractory cases, consider evaluating the patient’s environment for significant mold exposure that can be modified (Weak recommendation).
  • Consider adjunct leukotriene antagonists for some patients (Weak recommendation).
  • Follow-up could include imaging at 4-8 weeks and total serum IgE monitoring.
 2017 Aug;13(8):823-835. doi: 10.1080/1744666X.2017.1324298. Epub 2017 May 17.

Mold allergy: is it real and what do we do about it?

 

Abstract

fungi produce substances that contain pathogen-associated molecular patterns (pamps) and damage-associated molecular patterns (damps) which bind to pattern recognition receptors, stimulating innate immune responses in humans. they also produce allergens that induce production of specific ige. Areas covered: In this review we cover both innate and adaptive immune responses to fungi. Some fungal products can activate both innate and adaptive responses and in doing so, cause an intense and complex health effects. Methods of testing for fungal allergy and evidence for clinical treatment including environmental control are also discussed. In addition, we describe controversial issues including the role of Stachybotrys and mycotoxins in adverse health effects. Expert commentary: Concerns about long-term exposure to fungi have led some patients, attorneys and fungus advocates to promote fears about a condition that has been termed toxic mold syndrome. This syndrome is associated with vague symptoms and is believed to be due to exposure to mycotoxins, though this connection has not been proven. Ultimately, more precise methods are needed to measure both fungal exposure and the resulting health effects. Once that such methods become available, much of the speculation will be replaced by knowledge.