Introduction
Cystic fibrosis (CF) is a rare autosomal recessive disorder that affects
more than 85,000 individuals worldwide.1 Despite
significant advances in therapy, people with CF continue to experience
high rates of morbidity and mortality due to pulmonary
disease.2 People with CF are prone to inspissated
airway mucus with subsequent pulmonary endobronchitis caused by cystic
fibrosis transmembrane conductance regulator (CFTR ) protein
dysfunction that impairs chloride and bicarbonate secretion at the
airway surface layer. Individuals subsequently develop chronic airway
infections, episodic pulmonary exacerbations, and progressive airway
injury.3, 4 Bacterial pathogens such asPseudomonas aeruginosa are well known contributors to disease
progression and exacerbations. Fungi are also often isolated from lower
airway samples [sputum and bronchoalveolar lavage fluid (BAL)] but
their clinical impact is less well understood, especially when cultured
in the presence of concomitant bacteria.5
Fungal infection in people with CF has a wide spectrum of both detection
frequency and disease manifestations. Fungal detection may be transient,
intermittent, or chronic. Disease manifestations range from acute or
chronic fungal bronchitis with pulmonary exacerbation; sensitization to
fungal allergens; and allergic bronchopulmonary mycosis (ABPM) most
often caused by aspergillosis (allergic bronchopulmonary aspergillosis,
ABPA).5-9 Others with fungal positive cultures may
appear unaffected without worsening clinical signs or symptoms, or with
symptoms attributable to other causes. ABPA is at the severe end of
presentations and is a known allergic inflammatory process in reaction
to Aspergillus antigen causing airway mucus impaction and
obstruction.
Despite the possible associations, detection of fungus is not a
requirement for an ABPA diagnosis.6, 10, 11 The impact
of persistent fungal infection in the absence of ABPA on disease
progression is less clear. Some studies have shown decrease in lung
function over time in people with CF and Aspergillus infection as
well as other worsening clinical outcomes.7 Other
studies, however, have shown little clinical difference in those with or
without fungi. 12 Fungal detection has also been
associated with P. aeruginosa co-infection and with inhaled
antibiotic treatments often used to treat Pseudomonas , possibly
due to changes in microbial competition within the
community. 13, 14 Despite these studies, the
contribution of fungi to CF lung disease progression remains under
debate with few clinical guidelines upon isolation. Thus, we conducted a
retrospective cohort study to compare clinical outcomes and disease
course between individuals with CF with and without frequent fungal
detection from airway samples, while accounting for chronic P.
aeruginosa infection and ABPA diagnosis.