Progress and challenges in fungal lung disease in cystic fibrosis

Hong, Gina

doi:10.1097/mcp.0000000000000921

Cited by 6 publications

(6 citation statements)

References 83 publications

(124 reference statements)

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“…It is worth noting that most BALF samples did not have fungal culture data available, which could be because the samples were collected before fungal culture was prevalent in clinical care. Inconsistencies in the use of fungal culture by CF status and institution further underscore the importance of establishing a standardized approach to detect airway fungi ( Hong, 2022 ).…”

Section: Discussionmentioning

confidence: 99%

Detection and identification of fungi in the lower airway of children with and without cystic fibrosis

et al. 2023

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IntroductionAirway infection and inflammation lead to the progression of obstructive lung disease in persons with cystic fibrosis (PWCF). However, cystic fibrosis (CF) fungal communities, known drivers of CF pathophysiology, remain poorly understood due to the shortcomings of traditional fungal culture. Our objective was to apply a novel small subunit rRNA gene (SSU-rRNA) sequencing approach to characterize the lower airway mycobiome in children with and without CF.MethodsBronchoalveolar lavage fluid (BALF) samples and relevant clinical data were collected from pediatric PWCF and disease control (DC) subjects. Total fungal load (TFL) was measured using quantitative PCR, and SSU-rRNA sequencing was used for mycobiome characterization. Results were compared across groups, and Morisita-Horn clustering was performed.Results161 (84%) of the BALF samples collected had sufficient load for SSU-rRNA sequencing, with amplification being more common in PWCF. BALF from PWCF had increased TFL and increased neutrophilic inflammation compared to DC subjects. PWCF exhibited increased abundance of Aspergillus and Candida, while Malassezia, Cladosporium, and Pleosporales were prevalent in both groups. CF and DC samples showed no clear differences in clustering when compared to each other or to negative controls. SSU-rRNA sequencing was used to profile the mycobiome in pediatric PWCF and DC subjects. Notable differences were observed between the groups, including the abundance of Aspergillus and Candida.DiscussionFungal DNA detected in the airway could represent a combination of pathogenic fungi and environmental exposure (e.g., dust) to fungus indicative of a common background signature. Next steps will require comparisons to airway bacterial communities.

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Section: Discussionmentioning

confidence: 99%

Detection and identification of fungi in the lower airway of children with and without cystic fibrosis

et al. 2023

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“…In addition, Af causes different host responses, with some individuals developing an allergic, Th-2-type response resulting in ABPA or Af sensitization, while others develop a neutrophilic response more typical of CF endobronchitis. While ABPA has a defined clinical presentation with standardized criteria for diagnosis and treatment, the impact of Af in a non-ABPA phenotype is less clear [ 18 ]. In addition, some of the criteria for ABPA diagnoses overlap with progression of the CF lung disease (e.g., bronchiectasis) leading to diagnostic uncertainty in some patients.…”

Section: Clinical Impact Of Af In Pwcfmentioning

confidence: 99%

“…A phenotype of the Af infection called fungal bronchitis has been described. Patients with this diagnosis may have recurrent positive fungal cultures and evidence of worsened disease (lung function decline, changes in CT findings), poor response to antibiotic treatment of exacerbation, exacerbation symptoms not attributable to other causes, or elevation in Af-specific IgG, but do not have evidence of a hypersensitivity response [ 18 , 23 ]. Treatment is often initiated with antifungals, although data around their efficacy is limited.…”

Section: Clinical Management Of Af Infections In Pwcfmentioning

confidence: 99%

“…While bacteria are the main culprits of infection and inflammatory response in the CF airway, many molds are implicated as also causing disease either by an infectious process or an allergic response. Aspergillus fumigatus (Af) is one of the most common molds isolated in airway samples from people with CF (pwCF) [ 15 , 16 , 17 , 18 ]. Despite its prevalence, few guidelines on the treatment of Af in pwCF exist and there is limited mechanistic understanding of why and how Af persists in the CF airway.…”

Section: Introductionmentioning

confidence: 99%

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

Poore

Zemanick

2023

Microorganisms

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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.

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“…Previous reviews have discussed fungal respiratory disease in immunocompetent patients [8], cystic fibrosis [9 ▪ ], and other chronic respiratory disorders [10 ▪ ]. Here we review IFRIs in the immunocompromised host, focussing on host susceptibility factors, clinical features and available diagnostic tools.…”

Section: Introductionmentioning

confidence: 99%

Diagnosis of invasive respiratory mycoses in the immunocompromised host

Houston

Wilson

Stone

2023

Current Opinion in Pulmonary Medicine

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Purpose of reviewThe burden of invasive fungal infection is increasing worldwide, largely due to a growing population at-risk. Most serious human fungal pathogens enter the host via the respiratory tract. Early identification and treatment of invasive fungal respiratory infections (IFRIs) in the immunocompromised host saves lives. However, their accurate diagnosis is a difficult challenge for clinicians and mortality remains high.Recent findingsThis article reviews IFRIs, focussing on host susceptibility factors, clinical presentation, and mycological diagnosis. Several new diagnostic tools are coming of age including molecular diagnostics and point-of-care antigen tests. As diagnosis of IFRI relies heavily on invasive procedures like bronchoalveolar lavage and lung biopsy, several novel noninvasive diagnostic techniques are in development, such as metagenomics, ‘volatilomics’ and advanced imaging technologies.SummaryWhere IFRI cannot be proven, clinicians must employ a ‘weights-of-evidence’ approach to evaluate host factors, clinical and mycological data. Implementation studies are needed to understand how new diagnostic tools can be best applied within clinical pathways. Differentiating invasive infection from colonization and identifying antifungal resistance remain key challenges. As our diagnostic arsenal expands, centralized clinical mycology laboratories and efforts to ensure access to new diagnostics in low-resource settings will become increasingly important.

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Progress and challenges in fungal lung disease in cystic fibrosis

Cited by 6 publications

References 83 publications

Detection and identification of fungi in the lower airway of children with and without cystic fibrosis

Detection and identification of fungi in the lower airway of children with and without cystic fibrosis

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

Diagnosis of invasive respiratory mycoses in the immunocompromised host

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