When should I suspect invasive pulmonary aspergillosis in my patient with COPD exacerbation?

Think of invasive pulmonary aspergillosis (IPA) in your patient when she or he has a COPD exacerbation that appears refractory to broad-spectrum antibiotics and high doses of steroids. Heighten your suspicion even more in patients with severe-steroid dependent COPD, presence of a new pulmonary infiltrate or isolation of Aspergillus spp from respiratory cultures. 1

It’s worth remembering that although dyspnea and bronchospasm are found in most COPD patients with IPA, in contrast to haematological patients, fever, chest pain and hemoptysis are usually absent in this patient population.1

Diagnosis of IPA in this patient population is challenging for several reasons including: 1. A definitive or “proven” diagnosis requires histopathologic evidence of Aspergillus invasion of lung tissue which is not possible without subjecting an already fragile patient to invasive procedures (eg, lung aspiration or biopsy); 2. In contrast to IPA in highly susceptible immunocompromised patients with cancer and recipients of hematopoietic stem cell transplants, standardized definition of IPA in patients with COPD is lacking; 1,3 and 3. Frequent colonization of the respiratory tract of COPD patients with Aspergillus spp (16.3 per 1000 COPD admission in 1 study) 4,5, makes it difficult to diagnose IPA based on cultures alone.

Aside from respiratory cultures, another non-invasive test, serum galactomannan (GM, a polysaccharide antigen that exists primarily in the cell walls of Aspergillus spp and released into the blood during its growth phase 6) may have some utility in suggesting IPA in COPD patients, albeit with a mediocre sensitivity (~30-60%) but respectable specificity (>80 %). In contrast, bronchoalveolar lavage fluid GM may have better sensitivity  (~75%-90%) with similar specificity as that of serum GM in the diagnosis of IPA in these patients 7-8

Bonus pearl: Did you know that the incidence of IPA appears to be increasing in COPD patients requiring ICU admission, with reported mortality rates of 67% to 100%? 7

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  1. Bulpa P, Dive A, Sibille Y. Invasive pulmonary aspergillosis in patients with chronic obstructive pulmonary disease. Eur Res J 2007;30:782-800. https://www.ncbi.nlm.nih.gov/pubmed/17906086
  2. Bulpa P, Bihin B, Dimopoulos G, et al. Which algorithm diagnoses invasive pulmonary aspergillosis best in ICU patietns with COPD? Eur Resir J 2017;50:1700532 https://www.ncbi.nlm.nih.gov/pubmed/28954783
  3. Barberan J, Garcia-Perez FJ, Villena V, et al. Development of aspergillosis in a cohort of non-neutropenic, non-transplant patients colonized by Aspergillus spp. BMC Infect Dis 2017;17:34. https://link.springer.com/article/10.1186/s12879-016-2143-5
  4. Guinea J, Torres-Narbona M, Gijon P, et al. Pulmonary aspergillosis in patients with chronic obstructive pulmonary disease: incidence, risk factors, and outcome. Clin Microbiol Infect 2010; 16:870-77. https://www.sciencedirect.com/science/article/pii/S1198743X14617432
  5. Blot Stijn I, Taccone FS, Van den Abeele A-M, et al. A clinical algorithm to diagnose invasive pulmonary aspergillosis in critically ill patients. Am J Respir Crit Care Med 202;186:56-64. https://www.atsjournals.org/doi/full/10.1164/rccm.201111-1978OC
  6. Pfeiffer CD, Fine JP, Safdar N. Diagnosis of invasive aspergillosis using a galactomannan assay: a meta-analysis. Clin Infect Dis 2006;42:1417-27. https://academic.oup.com/cid/article/42/10/1417/278148
  7. He H, Ding L, Sun B, et al. Role of galactomannan determinations in bronchoalveolar lavage fluid samples from critically ill patients with chronic obstructive pulmonary disease for the diagnosis of invasive pulmonary aspergillosis: a prospective study. Critical Care 2012;16:R138. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5066034/
  8. Zhou W, Li H, Zhang Y, et al. Diagnostic value of galactomannan antigen test in serum and bronchoalveolar lavage fluid samples from patients with nonneutropenic invasive pulmonary aspergillosis. J Clin Microbiol 2017;55:2153-61. https://www.ncbi.nlm.nih.gov/pubmed/28446576
When should I suspect invasive pulmonary aspergillosis in my patient with COPD exacerbation?