Poster: 44Reduced pathogens in bronchoalveolar lavage fluid from young children on elexacaftor/tezacaftor/ivacaftor

Abstract

Background

Elexacaftor/tezacaftor/ivacaftor (ETI) results in improved lung function and fewer pulmonary exacerbations for many people with cystic fibrosis (CF). In older children and adults with CF treated with ETI, airway infection with conventional pathogens are reduced but, particularly for those with preexisting chronic infection, airway infections often persist.[1] In young children with CF (CwCF), oropharyngeal cultures are used clinically to monitor for airway infections, but often do not correlate well with lower airway samples which are difficult to obtain.[2] BEGIN Part B (NCT04509050) is a longitudinal study of CwCF prior to and following initiation of ETI, including collection of bronchoalveolar lavage (BAL) fluid from a subset of participants. We sought to compare lower airway pathogens detected from BAL fluid before and after ETI initiation.

Elexacaftor/tezacaftor/ivacaftor (ETI) results in improved lung function and fewer pulmonary exacerbations for many people with cystic fibrosis (CF). In older children and adults with CF treated with ETI, airway infection with conventional pathogens are reduced but, particularly for those with preexisting chronic infection, airway infections often persist.[1] In young children with CF (CwCF), oropharyngeal cultures are used clinically to monitor for airway infections, but often do not correlate well with lower airway samples which are difficult to obtain.[2] BEGIN Part B (NCT04509050) is a longitudinal study of CwCF prior to and following initiation of ETI, including collection of bronchoalveolar lavage (BAL) fluid from a subset of participants. We sought to compare lower airway pathogens detected from BAL fluid before and after ETI initiation.

Methods

The BEGIN BAL sub-study is enrolling up to 20 CwCF at 5 study sites for research bronchoscopy with BAL during clinical stability prior to and one and two years following ETI initiation. Local microbiologic laboratories culture BAL samples for CF pathogens. Aliquots are shipped frozen to the CFF Microbiologic Outcomes Advancement Core (MOAC) Laboratory at University of Washington for future microbiome analyses and to the CFF Center for Biochemical Markers at Children’s Hospital Colorado for future inflammatory marker analysis. Oropharyngeal swabs and reagent and bronchoscope control aliquots are also collected and shipped frozen to MOAC. Data are presented as counts/percentages or mean ± standard deviation.

The BEGIN BAL sub-study is enrolling up to 20 CwCF at 5 study sites for research bronchoscopy with BAL during clinical stability prior to and one and two years following ETI initiation. Local microbiologic laboratories culture BAL samples for CF pathogens. Aliquots are shipped frozen to the CFF Microbiologic Outcomes Advancement Core (MOAC) Laboratory at University of Washington for future microbiome analyses and to the CFF Center for Biochemical Markers at Children’s Hospital Colorado for future inflammatory marker analysis. Oropharyngeal swabs and reagent and bronchoscope control aliquots are also collected and shipped frozen to MOAC. Data are presented as counts/percentages or mean ± standard deviation.

Results

The BEGIN BAL sub-study has enrolled 10 participants [mean age 4.5 ± 1.3 years] to date who underwent 27 bronchoscopies with BAL collection when clinically stable. Microbial culture results were available from nine BAL samples at baseline and eight BAL samples each at one and two years. At baseline, at least one CF pathogen was detected from 7/9 (78%) participants [S. aureus (4), H. influenzae (1), S. maltophilia (1), and Aspergillus spp. (1)]. At one and two years after initiating ETI, 3/8 (37.5%) and 1/8 (12.5%) of BAL samples had at least one CF pathogen detected: At one year, S. aureus (1) and H. influenzae (2); at year two, a single participant had methicillin-resistant S. aureus (MRSA), H. influenzae, and P. aeruginosa detected from BAL; only S. aureus was detected on that participant’s baseline BAL samples. Inflammatory marker analyses and microbiome studies are planned from banked aliquots.

The BEGIN BAL sub-study has enrolled 10 participants [mean age 4.5 ± 1.3 years] to date who underwent 27 bronchoscopies with BAL collection when clinically stable. Microbial culture results were available from nine BAL samples at baseline and eight BAL samples each at one and two years. At baseline, at least one CF pathogen was detected from 7/9 (78%) participants [S. aureus (4), H. influenzae (1), S. maltophilia (1), and Aspergillus spp. (1)]. At one and two years after initiating ETI, 3/8 (37.5%) and 1/8 (12.5%) of BAL samples had at least one CF pathogen detected: At one year, S. aureus (1) and H. influenzae (2); at year two, a single participant had methicillin-resistant S. aureus (MRSA), H. influenzae, and P. aeruginosa detected from BAL; only S. aureus was detected on that participant’s baseline BAL samples. Inflammatory marker analyses and microbiome studies are planned from banked aliquots.

Conclusions

Clinically stable CwCF who initiated ETI had a marked decrease in detection of lower airway pathogens from BAL following one and two years of therapy. Detection of MRSA and P. aeruginosa infections in one participant after two years of ETI highlights the need for continued vigilance. Future studies will include DNA-based analyses, which complement culture-based studies.

Clinically stable CwCF who initiated ETI had a marked decrease in detection of lower airway pathogens from BAL following one and two years of therapy. Detection of MRSA and P. aeruginosa infections in one participant after two years of ETI highlights the need for continued vigilance. Future studies will include DNA-based analyses, which complement culture-based studies.