:
and
often infect the airways in cystic fibrosis (CF). Because registry studies show higher prevalence of
versus
in older patients with CF, a common assumption is that
replaces
over time.
,
can ...outgrow and kill
. However, it is unknown how rapidly
replaces
in patients with CF.
: We studied a longitudinal cohort of children and adults with CF who had quantitative sputum cultures. We determined the abundance of
and
in cfu/ml. We determined the duration and persistence of infections and measured longitudinal changes in culture positivity and abundance for each organism.
: Between 2004 and 2017, 134 patients had ≥10 quantitative cultures, with median observation time of 10.15 years. One hundred twenty-four patients had at least one positive culture for
, and 123 had at least one positive culture for
. Both species had median abundance of >10
cfu/ml. Culture abundance was stable over time for both organisms. There was an increase in the prevalence of
/
coinfection but no decrease in
prevalence within individuals over time.
:
and
are abundant in CF sputum cultures. Contrary to common assumption, we found no pattern of replacement of
by
. Many patients with CF have durable long-term coinfection with these organisms. New strategies are needed to prevent and treat these infections.
Background
Cystic fibrosis transmembrane conductance regulator (CFTR) modulators have shown beneficial effects on both forced expiratory volume in 1 s (FEV1) and frequency of pulmonary exacerbations ...in people with cystic fibrosis (CF). These positive outcomes may be related to changes in bacterial colonization within the lungs. Elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) is the first triple therapy CFTR modulator approved for use in people with CF 6 years and older. This study aimed to determine the impact of ELX/TEZ/IVA on the isolation of Pseudomonas aeruginosa (Pa), methicillin‐resistant and methicillin‐susceptible Staphylococcus aureus (MRSA and MSSA, respectively) in respiratory cultures.
Methods
A retrospective chart review of the electronic medical record at the University of Iowa was completed for individuals 12 years and older taking ELX/TEZ/IVA for at least 12 months. The primary outcome was determined by assessing bacterial cultures pre‐ and postinitiation of ELX/TEZ/IVA. Baseline demographic and clinical characteristics were summarized using mean and standard deviation for continuous outcomes and count and percentage for categorical outcomes. Culture positivity for Pa, MSSA, and MRSA was compared among enrolled subjects between pre‐ and posttriple combination therapy periods using an exact McNemar's test.
Results
One hundred and twenty‐four subjects prescribed ELX/TEZ/IVA for at least 12 months met the requirements for inclusion within our analysis. Culture positivity for Pa, MSSA, and MRSA was approximately 54%, 33%, and 31%, respectively, for the pre‐ELX/TEZ/IVA period. Prevalence decreased to approximately 30%, 32%, and 24% (−24.2% p < 0.0001, −0.7% p = 1.00, and −6.5% p = 0.0963, respectively) post‐ELX/TEZ/IVA. The source of bacterial culture was predominantly sputum (70.2%) in the pre‐ELX/TEZ/IVA group, whereas a throat source (66.1%) was more common post‐ELX/TEZ/IVA.
Conclusions
ELX/TEZ/IVA treatment has an appreciable impact on the detection of common bacterial pathogens in CF respiratory cultures. While previous studies have found a similar effect with single and double CFTR modulator therapies, this is the first single‐center study to show the impact of triple therapy, ELX/TEZ/IVA, on bacterial isolation from airway secretions.
Chronic cavitary pulmonary aspergillosis (CCPA) has been associated with advanced lung diseases. Pulmonary sarcoidosis, a granulomatous inflammatory disorder, is associated with CCPA. We identified ...CCPA in 2% of cases in a large cohort of sarcoidosis patients. We found a lack of response to medical treatment and poor outcome in this subgroup.
Mycobacterial infections are uncommon in solid organ and hematopoietic stem cell transplant recipients but carry significant morbidity and mortality. Donor screening strategies for tuberculosis ...should be emphasized in high-risk populations. Both tuberculosis and nontuberculous mycobacterial infections can have pulmonary and extrapulmonary manifestations of infections. Recommended treatment regimens typically involve multiple drugs with significant adverse effects and drug interactions.
Obliterative bronchiolitis (OB) is a major cause of mortality after lung transplantation. Depletion of airway stem cells (SCs) may lead to fibrosis in OB.
Two major SC compartments in airways are ...submucosal glands (SMGs) and surface airway p63 (also known as TP63 tumor protein 63)-positive/K5 (also known as KRT5 keratin 5)-positive basal cells (BCs). We hypothesized that depletion of these SC compartments occurs in OB.
Ferret orthotopic left lung transplants were used as an experimental model of OB, and findings were corroborated in human lung allografts. Morphometric analysis was performed in ferret and human lungs to evaluate the abundance of SMGs and changes in the expression of phenotypic BC markers in control, lymphocytic bronchiolitis, and OB airways. The abundance and proliferative capacity of proximal and distal airway SCs was assessed using a clonogenic colony-forming efficiency assay.
Ferret allografts revealed significant loss of SMGs with development of OB. A progressive decline in p63
/K5
and increase in K5
/K14
and K14
BC phenotypes correlated with the severity of allograft rejection in large and small ferret airways. The abundance and proliferative capacity of basal SCs in large allograft airways declined with severity of OB, and there was complete ablation of basal SCs in distal OB airways. Human allografts mirrored phenotypic BC changes observed in the ferret model.
SMGs and basal SC compartments are depleted in large and/or small airways of lung allografts, and basal SC proliferative capacity declines with progression of disease and phenotypic changes. Global airway SC depletion may be a mechanism for pulmonary allograft failure.
Background:
It is unclear whether continuing anti-fibrotic therapy until the time of lung transplant increases the risk of complications in patients with idiopathic pulmonary fibrosis.
Objectives:
To ...investigate whether the time between discontinuation of anti-fibrotic therapy and lung transplant in patients with idiopathic pulmonary fibrosis affects the risk of complications.
Methods:
We assessed intra-operative and post-transplant complications among patients with idiopathic pulmonary fibrosis who underwent lung transplant and had been treated with nintedanib or pirfenidone continuously for ⩾ 90 days at listing. Patients were grouped according to whether they had a shorter (⩽ 5 medication half-lives) or longer (> 5 medication half-lives) time between discontinuation of anti-fibrotic medication and transplant. Five half-lives corresponded to 2 days for nintedanib and 1 day for pirfenidone.
Results:
Among patients taking nintedanib (n = 107) or pirfenidone (n = 190), 211 (71.0%) had discontinued anti-fibrotic therapy ⩽ 5 medication half-lives before transplant. Anastomotic and sternal dehiscence occurred only in this group (anastomotic: 11 patients 5.2%, p = 0.031 vs patients with longer time between discontinuation of anti-fibrotic medication and transplant; sternal: 12 patients 5.7%, p = 0.024). No differences were observed in surgical wound dehiscence, length of hospital stay, or survival to discharge between groups with a shorter versus longer time between discontinuation of anti-fibrotic therapy and transplant.
Conclusion:
Anastomotic and sternal dehiscence only occurred in patients with idiopathic pulmonary fibrosis who discontinued anti-fibrotic therapy < 5 medication half-lives before transplant. The frequency of other intra-operative and post-transplant complications did not appear to differ depending on when anti-fibrotic therapy was discontinued.
Registration:
clinicaltrials.gov NCT04316780: https://clinicaltrials.gov/ct2/show/NCT04316780
Chimeric antigen receptor T-cell therapy (CAR-T) has been used to treat refractory post-transplant lymphoproliferative disorder (PTLD) in solid organ transplant patients, including heart, kidney, ...liver, intestine, and pancreas. We report the use of CAR-T for treating refractory PTLD in a 73-year-old female who was 7 years post bilateral lung transplantation for idiopathic pulmonary fibrosis. We discuss the immunosuppression management in this patient, as well as her clinical course and outcome.
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