Infection, Allergy, and Inflammation: The Role of Aspergillus fumigatus in Cystic Fibrosis.

Aspergillus fumigatus (Af) is a mold frequently detected in airway samples from people with cystic fibrosis (pwCF). Abnormal airway mucus may allow Af to germinate, resulting in airway infection or an allergic response. While Af is known to increase morbidity in pwCF, individual responses and the degree of impact on lung disease vary. Improved approaches to diagnosis, treatment, and prevention of Af, particularly the persistent Af infection, are needed. This update highlights our current understanding of Af pathophysiology in the CF airway, the effects of Af on pwCF, and areas of research needed to improve clinical outcomes.

Cardiovascular complications in cystic fibrosis: A review of the literature.

Cystic fibrosis is a genetic disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, leading to dysfunction of the CFTR protein. CFTR dysfunction leads to disease in the respiratory and gastrointestinal systems. Disorders of the cardiovascular system in individuals with CF are usually attributed to secondary effects from progressive lung disease. However, CFTR has been localized to vascular endothelium and smooth muscle, suggesting that CFTR dysfunction may directly impact cardiovascular function. As treatments for CF improve and life-expectancy increases, the risk of vascular disease may increase in prevalence related to primary and secondary CFTR dysfunction, chronic systemic inflammation, nutritional health and hyperglycemia in individuals with CF related diabetes. Here we review the available literature on CF and the cardiovascular system, examining the secondary effects and evidence for direct CFTR dysfunction in the heart, aorta, pulmonary vessels, and vasculature, as well as future directions and treatment options.

Differing rates of fungi in sinonasal cultures from pediatric sinusitis patients.

OBJECTIVES: Pediatric chronic rhinosinusitis (PCRS) is a unique clinical entity and the underlying source of inflammation is unknown. Certain subgroups, such as children with nasal polyps and cystic fibrosis (CF) sinusitis are often recalcitrant to standard medical PCRS treatments that target bacterial inflammation. Fungal infection and allergy to fungal proteins drive inflammation in other airway diseases, resulting in chronic inflammation of both the upper and lower airways. However, there is limited understanding of the role of fungi in the pathophysiology of PCRS. The objective of this study is to define the frequency of fungal infection in pediatric CRS patients, hypothesizing that certain subgroups may have more frequent positive fungal sinus cultures than other subgroups of pediatric sinusitis. METHODS: Retrospective study of patients undergoing sinus surgery at a tertiary care pediatric hospital to determine the period prevalence of positive fungal cultures in subgroups of patients. RESULTS: 400 children from 2012 to 2019 were included. 265 patients had surgical culture results available. Of the 52 patients with CF 11 (21%) had positive fungal sinus cultures. Similarly, 28% of the 25 patients with non-CF nasal polyps had positive cultures. Only 8.2% of 110 CRS without polyps patients had positive cultures, significantly fewer than other subgroups (X2 (1, N = 240) = 17.22, p < 0.01). CONCLUSION: Children with CF and children with nasal polyps had more frequent positive fungal cultures than children without nasal polyps having sinus surgery. This confirms that pediatric CF and pediatric CRS with polyps represent unique populations to study the impact of fungal infection in CRS. Further research is required to determine if these fungi represent colonization or contribute to the inflammatory environment of the airways.

Clinical characteristics of people with cystic fibrosis and frequent fungal infection.

BACKGROUND: Individuals with cystic fibrosis (CF) and fungal airway infection may present with fungal bronchitis, allergic bronchopulmonary aspergillosis (ABPA) or may appear unaffected despite fungal detection. We sought to characterize people with CF with frequent detection of fungi from airway samples and determine clinical outcomes. METHODS: This retrospective study included individuals with CF with ≥4 lower airway cultures over a 2-year baseline period and ≥2 years of follow-up. We defined two groups: ≤1 positive fungus culture (rare) or ≥2 positive cultures during baseline (frequent). Clinical characteristics and outcomes were determined. RESULTS: Between 2004 and 2016, 294 individuals met inclusion with 62% classified as rare and 38% as frequent fungi during baseline. Median follow-up was 6 years (range: 2-9 years). Aspergillus fumigatus was the most common fungal species detected. Individuals with frequent fungi were older (13.7 vs. 11.7 years, p = .02) and more likely to have Stenotrophomonas maltophilia (35% vs. 17%, p < .001) at baseline, but did not differ in lung function or ABPA diagnosis. During follow-up, those with frequent fungi were more likely to have chronic Pseudomonas aeruginosa and S. maltophilia. Individuals with ABPA and frequent fungi had the highest rates of co-infection and co-morbidities, and a trend towards more rapid lung function decline. DISCUSSION: Fungal infection in CF was associated with frequent P. aeruginosa and S. maltophilia co-infection even in those without ABPA. Individuals with frequent fungi and ABPA had worse outcomes, highlighting the potential contribution of fungi to CF pulmonary disease.

Fungal Infection and Inflammation in Cystic Fibrosis.

Fungi are frequently recovered from lower airway samples from people with cystic fibrosis (CF), yet the role of fungi in the progression of lung disease is debated. Recent studies suggest worsening clinical outcomes associated with airway fungal detection, although most studies to date are retrospective or observational. The presence of fungi can elicit a T helper cell type 2 (Th-2) mediated inflammatory reaction known as allergic bronchopulmonary aspergillosis (ABPA), particularly in those with a genetic atopic predisposition. In this review, we discuss the epidemiology of fungal infections in people with CF, risk factors associated with development of fungal infections, and microbiologic approaches for isolation and identification of fungi. We review the spectrum of fungal disease presentations, clinical outcomes after isolation of fungi from airway samples, and the importance of considering airway co-infections. Finally, we discuss the association between fungi and airway inflammation highlighting gaps in knowledge and future research questions that may further elucidate the role of fungus in lung disease progression.

Potential pathogenicity of Inquilinus limosus in a pediatric patient with cystic fibrosis.

PRESENTATION: Patient is a 6-year-old male with CF, MRSA colonization, and pancreatic insufficiency that presented with worsening ppFEV1 and systemic symptoms despite multiple interventions. BAL grew NTM, Stenotrophomonas maltophilia, and Inquilinus limosus, a rare organism found in patients with CF. COURSE: I. limosus treatment was deferred. Despite treatment of other pathogens, symptoms worsened. I. limosus was targeted with meropenem, amikacin, and ciprofloxacin along with clindamycin for MRSA colonization. Within weeks, symptoms had resolved with ppFEV1 improvement. DISCUSSION: This case discusses the importance of a rare organism in the CF population. Targeting I. limosus was key to recovery, revealing its potential pathogenicity.