scholarly journals Monogenic gene variants in lung transplant recipients with usual interstitial pneumonia

2022 ◽  
pp. 00583-2021
Author(s):  
Christoffer Stark ◽  
Juha W. Koskenvuo ◽  
Antti Nykänen ◽  
Eija H. Seppälä ◽  
Samuel Myllykangas ◽  
...  
Keyword(s):  
Pulmonary Fibrosis ◽  
Acute Rejection ◽  
Disease Progression ◽  
Interstitial Pneumonia ◽  
Lung Transplant ◽  
Usual Interstitial Pneumonia ◽  
Gene Variants ◽  
Transplant Recipients ◽  
Allograft Dysfunction ◽  
Lung Transplant Recipients

Question addressed by the studyThe prevalence of monogenic disease-causing gene variants in lung-transplant recipients with idiopathic pulmonary fibrosis is not fully known. Their impact on clinical outcomes before and after transplantation requires more evidence.Patients and MethodsWe retrospectively performed sequence analysis of genes associated with pulmonary fibrosis in a cohort of 23 patients with histologically confirmed usual interstitial pneumonia that had previously undergone double lung transplantation. We evaluated the impact of confirmed molecular diagnoses on disease progression, clinical outcomes and incidence of acute rejection or chronic lung allograft dysfunction after transplantation.ResultsFifteen patients out of 23 (65%) had a variant in a gene associated with interstitial lung disease. Eleven patients (48%) received a molecular diagnosis, of which nine involved genes for telomerase function. Five diagnostic variants were found in the gene for Telomerase reverse transcriptase. Two of these variants, p.(Asp684Gly) and p.(Arg774*), seemed to be enriched in Finnish lung-transplant recipients. Disease progression and the incidence of acute rejection and chronic lung allograft dysfunction was similar between patients with telomere-related disease and the rest of the study population. The incidence of renal or bone marrow insufficiency or skin malignancies did not differ between the groups.Answer to the questionGenetic variants are common in lung transplant recipients with pulmonary fibrosis and are most often related to telomerase function. A molecular diagnosis for telomeropathy does not seem to impact disease progression or the risk of complications or allograft dysfunction after transplantation.

scholarly journals Detrimental Association of Hypogammaglobulinemia With Chronic Lung Allograft Dysfunction and Death Is Not Mitigated by On-Demand Immunoglobulin G Replacement After Lung Transplantation

2018 ◽  
Vol 29 (1) ◽  
pp. 18-25
Author(s):  
Alicia B. Lichvar ◽  
Christopher R. Ensor ◽  
Adriana Zeevi ◽  
Matthew R. Morrell ◽  
Joseph M. Pilewski ◽  
...  
Keyword(s):  
Lung Transplantation ◽  
Immunoglobulin G ◽  
Lung Transplant ◽  
Primary Outcome ◽  
Transplant Recipients ◽  
Chronic Lung Allograft Dysfunction ◽  
On Demand ◽  
Allograft Dysfunction ◽  
Group 2 ◽  
Lung Transplant Recipients

Background: Hypogammaglobulinemia (HGG), immunoglobulin G (IgG) <700 mg/dL, is associated with infections, chronic lung allograft dysfunction, and death following lung transplantation. This study evaluates the use of on-demand intravenous IgG in lung transplant recipients with HGG. Materials and Methods: This single-center retrospective cohort study of adult lung recipients evaluated 3 groups, no, untreated (u), or treated (t) HGG at first IgG administration or a matched time posttransplant. Primary outcome was freedom from allograft dysfunction. Secondary outcomes included development of advanced dysfunction, rejection, infection burden, and mortality. Results: Recipients included 484 (no HGG: 76, uHGG: 192, tHGG: 216). Freedom from chronic allograph dysfunction was highest in the non-HGG group 2 years post-enrollment (no HGG 77.9% vs uHGG 56.4% vs tHGG 52.5%; P = .002). Freedom from advanced dysfunction was significantly different 2 years post-enrollment (no HGG 90.5% vs uHGG 84.7% vs tHGG 75.4%; P = .017). Patients without HGG and those with uHGG had less mortality at 2 years post-enrollment (no HGG 84.2% vs uHGG 81.3% vs tHGG 64.8%; P < .001). Gram-negative pneumonias occurred more often in the tHGG group ( P = .02). Conclusions: Development of chronic lung allograft dysfunction, patient survival, rejection burden, and key infectious outcomes in lung transplant recipients were still problematic in the context of on-demand IgG therapy. Prospective studies are warranted.

scholarly journals Community-acquired Respiratory Viruses Are a Risk Factor for Chronic Lung Allograft Dysfunction

2018 ◽  
Vol 69 (7) ◽  
pp. 1192-1197 ◽  
Author(s):  
Maddalena Peghin ◽  
Ibai Los-Arcos ◽  
Hans H Hirsch ◽  
Gemma Codina ◽  
Víctor Monforte ◽  
...  
Keyword(s):  
Infectious Disease ◽  
Risk Factors ◽  
Acute Rejection ◽  
Respiratory Tract ◽  
Lower Respiratory Tract ◽  
Lung Transplant ◽  
Respiratory Viruses ◽  
Transplant Recipients ◽  
Independent Risk Factors ◽  
Lung Transplant Recipients

Abstract Background The relationship between community-acquired respiratory viruses (CARVs) and chronic lung allograft dysfunction (CLAD) in lung transplant recipients is still controversial. Methods We performed a prospective cohort study (2009–2014) in all consecutive adult patients (≥18 years) undergoing lung transplantation in the Hospital Universitari Vall d’Hebron (Barcelona, Spain). We systematically collected nasopharyngeal swabs from asymptomatic patients during seasonal changes, from patients with upper respiratory tract infectious disease, lower respiratory tract infectious disease (LRTID), or acute rejection. Nasopharyngeal swabs were analyzed by multiplex polymerase chain reaction. Primary outcome was to evaluate the potential association of CARVs and development of CLAD. Time-dependent Cox regression models were performed to identify the independent risk factors for CLAD. Results Overall, 98 patients (67 bilateral lung transplant recipients; 63.3% male; mean age, 49.9 years) were included. Mean postoperative follow-up was 3.4 years (interquartile range [IQR], 2.5–4.0 years). Thirty-eight lung transplant recipients (38.8%) developed CLAD, in a median time of 20.4 months (IQR, 12–30.4 months). In time-controlled multivariate analysis, CARV-LRTID (hazard ratio [HR], 3.00 [95% confidence interval {CI}, 1.52–5.91]; P = .002), acute rejection (HR, 2.97 [95% CI, 1.51–5.83]; P = .002), and cytomegalovirus pneumonitis (HR, 3.76 [95% CI, 1.23–11.49]; P = .02) were independent risk factors associated with developing CLAD. Conclusions Lung transplant recipients with CARVs in the lower respiratory tract are at increased risk to develop CLAD.

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