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.